Cytotoxic T-lymphocyte-inducing immunogens for prevention, treatment, and diagnosis of cancer

ABSTRACT

The present invention relates to compositions and methods for the prevention, treatment, and diagnosis of cancer, especially carcinomas, such as ovarian carcinoma. The invention discloses peptides, polypeptides, and polynucleotides that can be used to stimulate a CTL response against cancer.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of U.S. application Ser. No. 10/006,177, filed Dec. 4, 2001, and now U.S. Pat. No. 7,083,789, which claims priority from U.S. provisional application No. 60/251,022, filed Dec. 4, 2000, and U.S. provisional application No. 60/256,824, filed Dec. 20, 2000, the disclosures of which are all herein incorporated by reference in their entireties.

FIELD OF THE INVENTION

The present invention relates generally to the field of immunogens whose structures incorporate polypeptides comprising epitopic peptides derived from proteins expressed by cancer cells and to uses of said immunogens in eliciting cytotoxic T lymphocyte (CTL) responses for the diagnosis, prevention and treatment of cancer, preferably carcinoma, most preferably ovarian carcinoma.

BACKGROUND OF THE INVENTION

The mammalian immune system has evolved a variety of mechanisms to protect the host from cancerous cells, an important component of this response being mediated by cells referred to as T cells. Cytotoxic T lymphocytes (CTLs) are specialized T cells that function primarily by recognizing and killing cancerous cells or infected cells, but also by secreting soluble molecules referred to as cytokines that can mediate a variety of effects on the immune system.

Evidence suggests that immunotherapy designed to stimulate a tumor-specific CTL response would be effective in controlling cancer. For example, it has been shown that human CTLs recognize sarcomas (Slovin, S. F. et al., J. Immunol., 137:3042-3048, (1987)), renal cell carcinomas (Schendel, D. J. et al., J. Immunol., 151:4209-4220, (1993)), colorectal carcinomas (Jacob, L. et al., Int. J. Cancer, 71:325-332, (1997)), ovarian carcinomas (Loannides, C. G. et al., J. Immunol., 146:1700-1707, (1991)) (Peoples, G. E. et al., Surgery, 114:227-234, (1993)), pancreatic carcinomas (Peiper, M. et al., Eur. J. Immunol., 27:1115-1123, (1997); Wolfel, T. et al., Int. J. Cancer, 54:636-644, (1993)), squamous tumors of the head and neck (Yasumura, S. et al., Cancer Res., 53:1461-1468, (1993)), and squamous carcinomas of the lung (Slingluff, C. L. Jr et al., Cancer Res., 54:2731-2737, (1994); Yoshino, I. et al., Cancer Res., 54:3387-3390, (1994)). The largest number of reports of human tumor-reactive CTLs have concerned cancers (Boon, T. et al., Ann. Rev. Immunol., 12:337-365, (1994)). The ability of tumor-specific CTLs to mediate tumor regression, in both human (Rosenberg, S. A. et al., N. Engl. J. Med., 319:1676-1680, (1988)) and animal models (Celluzzi, C. M. et al., J. Exp. Med., 183:283-287, (1996); Mayordomo, J. I. et al., Nat. Med., 1:1297-1302, (1995); Zitvogel, L. et al., J. Exp. Med., 183:87-97, (1996)), suggests that methods directed at increasing CTL activity would likely have a beneficial effect with respect to tumor treatment.

In order for CTLs to kill or secrete cytokines in response to a cancer cell, the CTL must first recognize that cell as being cancerous. This process involves the interaction of the T cell receptor, located on the surface of the CTL, with what is generically referred to as an MHC-peptide complex which is located on the surface of the cancerous cell. MHC (major histocompatibility-complex)-encoded molecules have been subdivided into two types, and are referred to as class I and class II MHC-encoded molecules.

In the human immune system, MHC molecules are referred to as human leukocyte antigens (HLA). Within the MHC, located on chromosome six, are three different genetic loci that encode for class I MHC molecules. MHC molecules encoded at these loci are referred to as HLA-A, HLA-B, and HLA-C. The genes that can be encoded at each of these loci are extremely polymorphic, and thus, different individuals within the population express different class I MHC molecules on the surface of their cells. HLA-A1, HLA-A2, HLA-A3, HLA-B7, and HLA-B8 are examples of different class I MHC molecules that can be expressed from these loci. The present disclosure involves peptides that are associated with the HLA-A1, HLA-A2, or HLA-A11 molecules, HLA-A1 supertypes, HLA-A2 supertypes, and HLA-A11 supertypes and with the gene and protein that gives rise to these peptides. A supertype is a group of HLA molecules that present at least one shared epitope.

The peptides that associate with the MHC molecules can either be derived from proteins made within the cell, in which case they typically associate with class I MHC molecules (Rock, K. L. and Golde, U., Ann. Rev. Immunol., 17:739-779, (1999)) or they can be derived from proteins that are acquired from outside of the cell, in which case they typically associate with class II MHC molecules (Watts, C., Ann. Rev. Immunol., 15:821-850, (1997)). Peptides that evoke a cancer-specific CTL response most typically associate with class I MHC molecules. The peptides that associate with a class I MHC molecule are typically nine amino acids in length, but can vary from a minimum length of eight amino acids to a maximum of fourteen amino acids in length. A class I MHC molecule with its bound peptide, or a class II MHC molecule with its bound peptide, is referred to as an MHC-peptide complex.

The process by which intact proteins are degraded into peptides is referred to as antigen processing. Two major pathways of antigen processing occur within cells (Rock, K. L. and Golde, U., Ann. Rev. Immunol., 17:739-779, (1999); Watts, C., Ann. Rev. Immunol., 15:821-850, (1997)). One pathway, which is largely restricted to cells that are antigen presenting cells such as dendritic cells, macrophages, and B cells, degrades proteins that are typically phagocytosed or endocytosed into the cell. Peptides derived in this pathway typically bind to class II MHC molecules. A second pathway of antigen processing is present in essentially all cells of the body. This second pathway primarily degrades proteins that are made within the cells, and the peptides derived from this pathway primarily bind to class I MHC molecules. It is the peptides from this second pathway of antigen processing that are referred to herein. Antigen processing by this latter pathway involves polypeptide synthesis and proteolysis in the cytoplasm. The peptides produced are then transported into the endoplasmic reticulum of the cell, associate with newly synthesized class I MHC molecules, and the resulting MHC-peptide complexes are then transported to the cell surface. Peptides derived from membrane and secreted proteins have also been identified. In some cases these peptides correspond to the signal sequence of the proteins that are cleaved from the protein by the signal peptidase. In other cases, it is thought that some fraction of the membrane and secreted proteins are transported from the endoplasmic reticulum into the cytoplasm where processing subsequently occurs.

Once bound to the class I MHC molecule and displayed on the surface of a cell, the peptides are recognized by antigen-specific receptors on CTLs. Mere expression of the class I MHC molecule itself is insufficient to trigger the CTL to kill the target cell if the antigenic peptide is not bound to the class I MHC molecule. Several methods have been developed to identify the peptides recognized by CTL, each method relying on the ability of a CTL to recognize and kill only those cells expressing the appropriate class I MHC molecule with the peptide bound to it (Rosenberg, S. A., Immunity, 10:281-287, (1999)). Such peptides can be derived from a non-self source, such as a pathogen (for example, following the infection of a cell by a bacterium or a virus) or from a self-derived protein within a cell, such as a cancerous cell. Examples of sources of self-derived proteins in cancerous cells have been reviewed (Gilboa, E., Immunity, 11:263-270, (1999); Rosenberg, S. A., Immunity, 10:281-287, (1999)) and include: (i) mutated genes; (ii) aberrantly expressed genes such as an alternative open reading frame or through an intron-exon boundary; (iii) normal genes that are selectively expressed in only the tumor and the testis; and (iv) normal differentiation genes that are expressed in the tumor and the normal cellular counterpart.

Four different methodologies have typically been used for identifying the peptides that are recognized by CTLs. These are: (i) the genetic method; (2) motif analysis; (3) SErological analysis of REcombinant cDNA expression libraries (SEREX™); and (iv) the analytical chemistry approach or the Direct Identification of Relevant Epitopes for Clinical Therapeutics (DIRECT™).

The genetic method is an approach in which progressively smaller subsets of cDNA libraries from tumor cells are transfected into cells that express the appropriate MHC molecule but not the tumor-specific epitope. The molecular clones encoding T cell epitopes are identified by their ability to reconstitute tumor specific T cell recognition of transfected cells. The exact T cell epitope is then identified by a combination of molecular subcloning and the use of synthetic peptides based on the predicted amino acid sequence. Such methods, however, are susceptible to inadvertent identification of cross-reacting peptides, and are not capable of identifying important post-translational modifications.

Motif analysis involves scanning a protein for peptides containing known class I MHC binding motifs, followed by synthesis and assay of the predicted peptides for their ability to be recognized by tumor-specific CTL. This approach requires prior knowledge of the protein from which the peptides are derived. This approach is also greatly hampered by the fact that not all of the predicted peptide epitopes are presented on the surface of a cell (Yewdell, J. W. and Bennink, J. R., Ann. Rev. Immunol., 17:51-88, (1999)), thus additional experimentation is required to determine which of the predicted epitopes is useful.

The SEREX™ approach relies on using antibodies in the serum of cancer patients to screen cDNA expression libraries for a clone that expresses a protein recognized by the antibody. This methodology presumes that an antibody response will necessarily have developed in the presence of a T cell response, and thus, the identified clone is good candidate to encode a protein that can be recognized by T cells.

DIRECT™ involves a combination of cellular immunology and mass spectrometry. This approach involves the actual identification of CTL epitopes by sequencing the naturally occurring peptides associated with class I MHC molecules. In this approach, cells are first lysed in a detergent solution, the peptides associated with the class I MHC molecules are purified, and the peptides fractionated by high performance liquid chromatography (HPLC). The peptides are then used to reconstitute recognition by tumor-specific CTLs on a non-tumor cell expressing the appropriate MHC molecules. Sequencing is readily performed by tandem mass spectrometry (Henderson, R. A. et al., Proc. Natl. Acad. Sci. U.S.A, 90:10275-10279, (1993); Hogan, K. T. et al., Cancer Res., 58:5144-5150, (1998); Hunt, D. F. et al., Science, 255:1261-1263, (1992); Slingluff, C. L. Jr et al., J. Immunol., 150:2955-2963, (1993)).

Immunization with cancer-derived, class I MHC-encoded molecule-associated peptides, or with a precursor polypeptide or protein that contains the peptide, or with a gene that encodes a polypeptide or protein containing the peptide, are forms of immunotherapy that can be employed in the treatment of cancer. These forms of immunotherapy require that immunogens be identified so that they can be formulated into an appropriate vaccine. Although a variety of cancer-derived antigens have been identified (Rosenberg, S. A., Immunity, 10:281-287, (1999)), not all of these are appropriate for broad-based immunotherapy as the expression of some peptides is limited to the tumor derived from a specific patient. Furthermore, the number of class I MHC molecules from which tumor-derived peptides have been discovered is largely restricted to HLA-A2. Thus, it would be useful to identify additional peptides that complex with class I MHC molecules other than HLA-A2. Such peptides would be particularly useful in the treatment of cancer patients who do not express the HLA-A2 molecule, HLA-A1 or HLA-A11 antigens, HLA-A1 supertypes, HLA-A2 supertypes and HLA-A11 supertypes, for example. It is also particularly useful to identify antigenic peptides that are derived from different original proteins, even if the derived peptides associate with the same class I MHC molecule. Because an active immune response can result in the outgrowth of tumor cells that have lost the expression of a particular precursor protein for a given antigenic peptide, it is advantageous to stimulate an immune response against peptides derived from more than one protein, as the chances of the tumor cell losing the expression of both proteins is the multiple of the chances of losing each of the individual proteins.

SUMMARY OF THE INVENTION

The present invention relates to Immunogens comprising polypeptides with amino acid sequences comprising epitopic sequences selected from the sequences of SEQ ID NO: 1-791 and 1514-1533 and which immunogens facilitate a cytotoxic T lymphocyte (CTL)-mediated immune response against cancers. The present invention also relates to nucleic acid molecules that encode for the polypeptides and/or the full length proteins from which the polypeptides are derived, of such immunogens, and which can also be used to facilitate an immune response against cancer.

The present invention provides compositions comprising the immunogen described herein, and polynucleotides that direct the synthesis of such polypeptides, whereby the oligopeptides and polypeptides of such immunogens are capable of inducing a CTL response against cells expressing a protein comprising an epitopic sequence of at least one of SEQ ID NO: 1-791 and 1514-1533. The cells are usually cancer cells, preferably carcinoma cells, most preferably ovarian carcinomas expressing such proteins.

The present invention further relates to polynucleotides comprising the gene coding for a polypeptide of the immunogens disclosed herein.

The present invention also provides methods that comprise contacting a lymphocyte, especially a CTL, with an immunogen of the invention under conditions that induce a CTL response against a tumor cell, and more specifically against a cancer cell. The methods may involve contacting the CTL with the immunogenic peptide in vivo, in which case the peptides, polypeptides, and polynucleotides of the invention are used as vaccines, and will be delivered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the immunogen, typically along with an adjuvant or one or more cytokines.

Alternatively, the immunogens of the present invention can be used to induce a CTL response in vitro. The generated CTL can then be introduced into a patient with cancer, more specifically cancer, colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, or prostate carcinoma. Alternatively, the ability to generate CTL in vitro could serve as a diagnostic for cancer generally, including colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, or prostate carcinoma.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

As used herein and except as noted otherwise, all terms are defined as given below.

The term “peptide” is used herein to designate a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids. The peptides are typically 9 amino acids in length, but can be as short as 8 amino acids in length, and as long as 14 amino acids in length.

The term “oligopeptide” is used herein to designate a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids. The length of the oligopeptide is not critical to the invention as long as the correct epitope or epitopes are maintained therein. The oligopeptides are typically less than about 30 amino acid residues in length, and greater than about 14 amino acids in length.

The term “polypeptide” designates a series of amino acid residues, connected one to the other typically by peptide bonds between the alpha-amino and carbonyl groups of the adjacent amino acids. The length of the polypeptide is not critical to the invention as long as the correct epitopes are maintained. In contrast to the terms peptide or oligopeptide, the term polypeptide is meant to refer to protein molecules of longer than about 30 residues in length.

A peptide, oligopeptide, protein, or polynucleotide coding for such a molecule is “immunogenic” (and thus an “immunogen” within the present invention) if it is capable of inducing an immune response. In the case of the present invention, immunogenicity is more specifically defined as the ability to induce a CTL-mediated response. Thus, an “immunogen” would be a molecule that is capable of inducing an immune response, and in the case of the present invention, a molecule capable of inducing a CTL response.

A T cell “epitope” is a short peptide molecule that binds to a class I or II MHC molecule and that is subsequently recognized by a T cell. T cell epitopes that bind to class I MHC molecules are typically 8-14 amino acids in length, and most typically 9 amino acids in length. T cell epitopes that bind to class II MHC molecules are typically 12-20 amino acids in length. In the case of epitopes that bind to class II MHC molecules, the same T cell epitope may share a common core segment, but differ in the length of the carboxy- and amino-terminal flanking sequences due to the fact that ends of the peptide molecule are not buried in the structure of the class II MHC molecule peptide-binding cleft as they are in the class I MHC molecule peptide-binding cleft.

There are three different genetic loci that encode for class I MHC molecules: HLA-A, HLA-B, and HLA-C. HLA-A1, HLA-A2, and HLA-A11 are examples of different class I MHC molecules that can be expressed from these loci. The present invention also involves peptides that are associated with HLA-A1 supertypes, HLA-A2 supertypes, and HLA-A11 supertypes. A supertype is a group of HLA molecules that present at least one shared epitope. MHC molecule peptides that have been found to bind to one member of the MHC allele supertype family (A1 for example) are thought to be likely to bind to other members of the same supertype family (A32 for example; see Table 1, below.

TABLE 1 Supertype Motif Genotypes A1 x[TI(SVLM)] A*0101, A*0102, A*2501, A*2601, A*2604, xxxxxx[WFY] A*3201, A*3601, A*4301, A*8001 A2 x[LIVMATQ] A*0201, A*0202, A*0203, A*0204, A*0205, xxxxxx[LIVMAT] A*0206, A*0207, A*6802, A*6901 A3 x[AILMVST] A*0301, A*1101, A*3101, A*3301, A*6801 xxxxxx[RK] A24 x[YF(WIVLMT)] A*2301, A*2402, A*2403, A*2404, A*3001, xxxxxx[FI(YWLM)] A*3002, A*3003 B7 x[P]xxxxxx B*0702, B*0703, B*0704, B*0705, B*1508, B*3501, [ALIMVFWY] B*3502, B*3503, B*51, B*5301, B*5401, B*5501, B*5502, B*5601, B*5602, B*6701, B*7801 B27 x[RKH]xxxxxx B*1401, B*1402, B*1503, B*1509, B*1510, B*1518, [FLY(WMI)] B*2701, B*2702, B*2703, B*2704, B*2705, B*2706, B*2707, B*2708, B*3801, B*3802, B*3901, B*3902, B*3903, B*3904, B*4801, B*4802, B*7301 B44 x[E(D)]xxxxxx B*18, B*3701, B*4001, B*4006, B*4101, B*4402, [FWYLIMVA] B*4403, B*4501, B*4901, B*5001 B58 x[AST]xxxxxx B*1516, B*1517, B*5701, B*5702, B*58 [FWY(LIV)] B62 x[QL(IVMP)] B*1301, B*1302, B*1501, B*1502, B*1506, B*1512, xxxxxx[FWY(MIV)] B*1513, B*1514, B*1519, B*1521, B*4601, B*52

As used herein, reference to a DNA sequence includes both single stranded and double stranded DNA. Thus, the specific sequence, unless the context indicates otherwise, refers to the single strand DNA of such sequence, the duplex of such sequence with its complement (double stranded DNA) and the complement of such sequence.

The term “coding region” refers to that portion of a gene which either naturally or normally codes for the expression product of that gene in its natural genomic environment, i.e., the region coding in vivo for the native expression product of the gene. The coding region can be from a normal, mutated or altered gene, or can even be from a DNA sequence, or gene, wholly synthesized in the laboratory using methods well known to those of skill in the art of DNA synthesis.

The term “nucleotide sequence” refers to a heteropolymer of deoxyribonucleotides. The nucleotide sequence encoding for a particular peptide, oligopeptide, or polypeptide may be naturally occurring or they may be synthetically constructed. Generally, DNA segments encoding the peptides, polypeptides, and proteins of this invention are assembled from cDNA fragments and short oligonucleotide linkers, or from a series of oligonucleotides, to provide a synthetic gene which is capable of being expressed in a recombinant transcriptional unit comprising regulatory elements derived from a microbial or viral operon.

The term “expression product” means that polypeptide or protein that is the natural translation product of the gene and any nucleic acid sequence coding equivalents resulting from genetic code degeneracy and thus coding for the same amino acid(s).

The term “fragment,” when referring to a coding sequence, means a portion of DNA comprising less than the complete coding region whose expression product retains essentially the same biological function or activity as the expression product of the complete coding region.

The term “DNA segment” refers to a DNA polymer, in the form of a separate fragment or as a component of a larger DNA construct, which has been derived from DNA isolated at least once in substantially pure form, i.e., free of contaminating endogenous materials and in a quantity or concentration enabling identification, manipulation, and recovery of the segment and its component nucleotide sequences by standard biochemical methods, for example, by using a cloning vector. Such segments are provided in the form of an open reading frame uninterrupted by internal nontranslated sequences, or introns, which are typically present in eukaryotic genes. Sequences of non-translated DNA may be present downstream from the open reading frame, where the same do not interfere with manipulation or expression of the coding regions.

The term “primer” means a short nucleic acid sequence that is paired with one strand of DNA and provides a free 3′OH end at which a DNA polymerase starts synthesis of a deoxyribonucleotide chain.

The term “promoter” means a region of DNA involved in binding of RNA polymerase to initiate transcription.

The term “open reading frame (ORF)” means a series of triplets coding for amino acids without any termination codons and is a sequence (potentially) translatable into protein.

The term “isolated” means that the material is removed from its original environment (e.g., the natural environment if it is naturally occurring). For example, a naturally-occurring polynucleotide or polypeptide present in a living animal is not isolated, but the same polynucleotide or polypeptide, separated from some or all of the coexisting materials in the natural system, is isolated. Such polynucleotides could be part of a vector and/or such polynucleotides or polypeptides could be part of a composition, and still be isolated in that such vector or composition is not part of its natural environment.

The polynucleotides, and recombinant or immunogenic polypeptides, disclosed in accordance with the present invention may also be in “purified” form. The term “purified” does not require absolute purity; rather, it is intended as a relative definition, and can include preparations that are highly purified or preparations that are only partially purified, as those terms are understood by those of skill in the relevant art. For example, individual clones isolated from a cDNA library have been conventionally purified to electrophoretic homogeneity. Purification of starting material or natural material to at least one order of magnitude, preferably two or three orders, and more preferably four or five orders of magnitude is expressly contemplated. Furthermore, the claimed polypeptide which has a purity of preferably 0.001%, or at least 0.01% or 0.1%; and even desirably 1% by weight or greater is expressly contemplated.

The nucleic acids and polypeptide expression products disclosed according to the present invention, as well as expression vectors containing such nucleic acids and/or such polypeptides, may be in “enriched form.” As used herein, the term “enriched” means that the concentration of the material is at least about 2, 5, 10, 100, or 1000 times its natural concentration (for example), advantageously 0.01%, by weight, preferably at least about 0.1% by weight. Enriched preparations of about 0.5%, 1%, 5%, 10%, and 20% by weight are also contemplated. The sequences, constructs, vectors, clones, and other materials comprising the present invention can advantageously be in enriched or isolated form.

The term “active fragment” means a fragment that generates an immune response (i.e., has immunogenic activity) when administered, alone or optionally with a suitable adjuvant, to an animal, such as a mammal, for example, a rabbit or a mouse, and also including a human, such immune response taking the form of stimulating a CTL response within the recipient animal, such as a human. Alternatively, the “active fragment” may also be used to induce a CTL response in vitro.

As used herein, the terms “portion,” “segment,” and “fragment,” when used in relation to polypeptides, refer to a continuous sequence of residues, such as amino acid residues, which sequence forms a subset of a larger sequence. For example, if a polypeptide were subjected to treatment with any of the common endopeptidases, such as trypsin or chymotrypsin, the oligopeptides resulting from such treatment would represent portions, segments or fragments of the starting polypeptide. This means that any such fragment will necessarily contain as part of its amino acid sequence a segment, fragment or portion, that is substantially identical, if not exactly identical, to a sequence of SEQ ID NO: 792-1513, which correspond to the naturally occurring, or “parent” proteins of the SEQ ID NO: 1-791 and 1514-1533. When used in relation to polynucleotides, such terms refer to the products produced by treatment of said polynucleotides with any of the common endonucleases.

In accordance with the present invention, the term “percent identity” or “percent identical,” when referring to a sequence, means that a sequence is compared to a claimed or described sequence after alignment of the sequence to be compared (the “Compared Sequence”) with the described or claimed sequence (the “Reference Sequence”). The Percent Identity is then determined according to the following formula: Percent Identity=100[1−(C/R)] wherein C is the number of differences between the Reference Sequence and the Compared Sequence over the length of alignment between the Reference Sequence and the Compared Sequence wherein (i) each base or amino acid in the Reference Sequence that does not have a corresponding aligned base or amino acid in the Compared Sequence and (ii) each gap in the Reference Sequence and (iii) each aligned base or amino acid in the Reference Sequence that is different from an aligned base or amino acid in the Compared Sequence, constitutes a difference; and R is the number of bases or amino acids in the Reference Sequence over the length of the alignment with the Compared Sequence with any gap created in the Reference Sequence also being counted as a base or amino acid.

If an alignment exists between the Compared Sequence and the Reference Sequence for which the percent identity as calculated above is about equal to or greater than a specified minimum Percent Identity then the Compared Sequence has the specified minimum percent identity to the Reference Sequence even though alignments may exist in which the herein above calculated Percent Identity is less than the specified Percent Identity.

The present invention relates generally to immunogens and immunogenic compositions, and methods of use therefore, for the prevention, treatment, and diagnosis of cancer, especially carcinomas, including ovarian carcinomas. Disclosed according to the invention are immunogens comprising proteins or polypeptides whose amino acid sequences comprises one or more epitopic oligopeptides with sequences selected from the group SEQ ID NO: 1-791 and 1514-1533. In addition, the invention further relates to polynucleotides that can be used to stimulate a CTL response against cancer, and more specifically carcinoma, especially ovarian carcinomas.

In accordance with the present invention there are disclosed specific oligopeptide sequences with amino acid sequences shown in SEQ ID NO: 1-791 and 1514-1533, which represent epitopic peptides (i.e. immunogenic oligopeptide sequences) of at least about 8 amino acids in length, preferably about 9 amino acids in length (i.e., nonapeptides), and no longer than about 10 amino acids in length and present as part of a larger structure, such as a polypeptide or full length protein.

The polypeptides forming the immunogens of the present invention have amino acid sequences that comprise at least one stretch, possibly two, three, four, or more stretches of about 8 to 10 residues in length and which stretches differ in amino acid sequence from the sequences of SEQ ID NO: 1-791 and 1514-1533 by no more than about 1 amino acid residue, preferably a conservative amino acid residue, especially amino acids of the same general chemical character, such as where they are hydrophobic amino acids.

Said polypeptides can be of any desired length so long as they have immunogenic activity in that they are able, under a given set of desirable conditions, to elicit in vitro or in vivo the activation of cytotoxic T lymphocytes (CTLs) (i.e., a CTL response) against a presentation of a cancer specific protein, especially a carcinoma or sarcoma specific protein, most especially MAGE D, MAGE 4, MFG-E8 or human retinoblastoma-like protein, especially when such proteins are presented along with MHC-1 proteins, such as where said proteins are presented in vitro or in vivo by an antigen presenting cell (APC). The proteins and polypeptides forming the immunogens of the present invention can be naturally occurring or may be synthesized chemically. According to the present invention the polypeptides may comprise at least one of SEQ ID NO: 792-1513.

The present invention is also directed to an isolated polypeptide, especially one having immunogenic activity, the sequence of which comprises within it one or more stretches comprising any 2 or more of the sequences of SEQ ID NO: 1-791 and 1514-1533 and in any relative quantities and wherein said sequences may differ by one amino acid residues from the sequences of SEQ ID NO: 1-791 and 1514-1533 in any given stretch of 8 to 10 amino acid residues. Thus, within the present invention, by way of a non-limiting example only, such polypeptide may contain as part of its amino acid sequence, nonapeptide fragments having up to 8 amino acids identical to a sequence of SEQ ID NO: 1-4 such that the polypeptide comprises, in a specific embodiment, 2 segments with at least 8 residues identical to SEQ ID NO: 1 and one segment with at least 8 residues identical to SEQ ID NO: 3. In other embodiments, other combinations and permutations of the epitopic sequences disclosed herein may be part of an immunogen of the present invention or of such a polypeptide so long as any such polypeptide comprises at least 2 such epitopes, whether such epitopes are different or the same. Thus, in a specific embodiment, a polypeptide of the present invention may comprise 2 copies of the sequence of SEQ ID NO: 2 at some point or points within its length. Of course, any combinations and permutations of the epitopes disclosed herein, as long as they are present at least two in number in such polypeptides, are expressly contemplated.

All of the epitopic peptides of SEQ ID NO: 1-791 and 1514-1533 are derived from proteins expressed by cancer cells and sequences and were identified through the method of Automated High Through-put Sequencing (HTPS). Accordingly, SEQ ID NO: 792-1513 are polypeptides that comprise at least one of SEQ ID NO: 1-791 and 1514-1533.

Oligopeptides as disclosed herein may themselves be prepared by methods well known to those skilled in the art. (Grant, G. A., Synthetic Peptides: A User's Guide, 1992, W. H. Freeman and Company, New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York).

Besides the sequences of SEQ ID NO:1-791 and 1514-1533, the proteins and polypeptides forming the immunogens of the present invention may also comprise one or more other immunogenic amino acid stretches known to be associated with cancer, and more specifically with carcinomas and melanomas, including colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, or prostate carcinoma, and which may stimulate a CTL response whereby the immunogenic peptides associate with HLA-A1 or HLA-A11, or HLA-A2, or another class I MHC (i.e., MHC-1) molecule.

The immunogens of the present invention can be in the form of a composition of one or more of the different immunogens and wherein each immunogen is present in any desired relative abundance. Such compositions can be homogeneous or heterogeneous with respect to the individual immunogenic peptide components present therein, having only one or more than one of such peptides.

The oligopeptides and polypeptides useful in practicing the present invention may be derived by fractionation of naturally occurring proteins by methods such as protease treatment, or they may be produced by recombinant or synthetic methodologies that are well known and clear to the skilled artisan (Ausubel, F. M. et al, Current Protocols in Molecular Biology, 1999, John Wiley & Sons, Inc., New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York; Molecular Cloning: A Laboratory Manual, 1989, Cold Spring Harbor Laboratory Press, Cold Spring Harbor). The polypeptide may comprise a recombinant or synthetic polypeptide that comprises at least one of SEQ ID NO: 1-791 and 1514-1533 which sequences may also be present in multiple copies. Thus, oligopeptides and polypeptides of the present invention may have one, two, three, or more such immunogenic peptides within the amino acid sequence of said oligopeptides and polypeptides, and said immunogenic peptides, or epitopes, may be the same or may be different, or may have any number of such sequences wherein some of them are identical to each other in amino acid sequence while others within the same polypeptide sequence are different from each other and said epitopic sequences may occur in any order within said immunogenic polypeptide sequence. The location of such sequences within the sequence of a polypeptide forming an immunogen of the invention may affect relative immunogenic activity. In addition, immunogens of the present invention may comprise more than one protein comprising the amino acid sequences disclosed herein. Such polypeptides may be part of a single composition or may themselves be covalently or non-covalently linked to each other.

The immunogenic peptides disclosed herein may also be linked directly to, or through a spacer or linker to: an immunogenic carrier such as serum albumin, tetanus toxoid, keyhole limpet hemocyanin, dextran, or a recombinant virus particle; an immunogenic peptide known to stimulate a T helper cell type immune response; a cytokine such as interferon gamma or GMCSF; a targeting agent such as an antibody or receptor ligand; a stabilizing agent such as a lipid; or a conjugate of a plurality of epitopes to a branched lysine core structure, such as the so-called “multiple antigenic peptide” described in (Posneft, D. N. et al., J. Biol. Chem., 263:1719-1725, (1988)); a compound such as polyethylene glycol to increase the half life of the peptide; or additional amino acids such as a leader or secretory sequence, or a sequence employed for the purification of the mature sequence. Spacers and linkers are typically comprised of relatively small, neutral molecules, such as amino acids and which are substantially uncharged under physiological conditions. Such spacers are typically selected from the group of nonpolar or neutral polar amino acids, such as glycine, alanine, serine and other similar amino acids. Such optional spacers or linkers need not be comprised of the same residues and thus may be either homo- or hetero-oligomers. When present, such linkers will commonly be of length at least one or two, commonly 3, 4, 5, 6, and possibly as much as 10 or even up to 20 residues (in the case of amino acids). In addition, such linkers need not be composed of amino acids but any oligomeric structures will do as well so long as they provide the correct spacing so as to optimize the desired level of immunogenic activity of the immunogens of the present invention. The immunogen may therefore take any form that is capable of eliciting a CTL response.

In addition, the immunogenic peptides of the present invention may be part of an immunogenic structure via attachments other than conventional peptide bonds. Thus, any manner of attaching the peptides of the invention to an immunogen of the invention, such as an immunogenic polypeptide as disclosed herein, could provide an immunogenic structure as claimed herein. Thus, immunogens, such as proteins of the invention, are structures that contain the peptides disclosed according to the present invention but such immunogenic peptides may not necessarily be attached thereto by the conventional means of using ordinary peptide bounds. The immunogens of the present invention simply contain such peptides as part of their makeup, but how such peptides are to be combined to form the final immunogen is left to the talent and imagination of the user and is in no way restricted or limited by the disclosure contained herein.

The peptides that are naturally processed and bound to a class I MHC molecule, and which are recognized by a tumor-specific CTL, need not be the optimal peptides for stimulating a CTL response. See, for example, (Parkhurst, M. R. et al., J. Immunol., 157:2539-2548, (1996); Rosenberg, S. A. et al., Nat. Med., 4:321-327, (1998)). Thus, there can be utility in modifying a peptide, such that it more readily induces a CTL response. Generally, peptides may be modified at two types of positions. The peptides may be modified at amino acid residues that are predicted to interact with the class I MHC molecule, in which case the goal is to create a peptide that has a higher affinity for the class I MHC molecule than does the original peptide. The peptides can also be modified at amino acid residues that are predicted to interact with the T cell receptor on the CTL, in which case the goal is to create a peptide that has a higher affinity for the T cell receptor than does the original peptide. Both of these types of modifications can result in a variant peptide that is related to an original peptide, but which is better able to induce a CTL response than is the original peptide. As used herein, the term “original peptide” means an oligopeptide with the amino acid sequence selected from SEQ ID NO: 1-791 and 1514-1533.

The original peptides disclosed herein can be modified by the substitution of one or more residues at different, possibly selective, sites within the peptide chain. Such substitutions may be of a conservative nature, for example, where one amino acid is replaced by an amino acid of similar structure and characteristics, such as where a hydrophobic amino acid is replaced by another hydrophobic amino acid. Even more conservative would be replacement of amino acids of the same or similar size and chemical nature, such as where leucine is replaced by isoleucine. In studies of sequence variations in families of naturally occurring homologous proteins, certain amino acid substitutions are more often tolerated than others, and these are often show correlation with similarities in size, charge, polarity, and hydrophobicity between the original amino acid and its replacement, and such is the basis for defining “conservative substitutions.”

Conservative substitutions are herein defined as exchanges within one of the following five groups: Group 1—small aliphatic, nonpolar or slightly polar residues (Ala, Ser, Thr, Pro, Gly); Group 2—polar, negatively charged residues and their amides (Asp, Asn, Glu, Gln); Group 3—polar, positively charged residues (His, Arg, Lys); Group 4—large, aliphatic, nonpolar residues (Met, Leu, lie, Val, Cys); and Group 4—large, aromatic residues (Phe, Tyr, Trp).

Less conservative substitutions might involve the replacement of one amino acid by another that has similar characteristics but is somewhat different in size, such as replacement of an alanine by an isoleucine residue. Highly nonconservative replacements might involve substituting an acidic amino acid for one that is polar, or even for one that is basic in character. Such radical substitutions cannot, however, be dismissed as potentially ineffective since chemical effects are not totally predictable and radical substitutions might well give rise to serendipitous effects not otherwise predictable from simple chemical principles.

Of course, such substitutions may involve structures other than the common L-amino acids. Thus, D-amino acids might be substituted for the L-amino acids commonly found in the antigenic peptides of the invention and yet still be encompassed by the disclosure herein. In addition, amino acids possessing non-standard R groups (i.e., R groups other than those found in the common 20 amino acids of natural proteins) may also be used for substitution purposes to produce immunogens and immunogenic polypeptides according to the present invention.

If substitutions at more than one position are found to result in a peptide with substantially equivalent or greater antigenic activity as defined below, then combinations of those substitutions will be tested to determine if the combined substitutions result in additive or syngeneic effects on the antigenicity of the peptide. At most, no more than 4 positions within the peptide would simultaneously be substituted.

Based on cytotoxicity assays, an epitope is considered substantially identical to the reference peptide if it has at least 10% of the antigenic activity of the reference peptide as defined by the ability of the substituted peptide to reconstitute the epitope recognized by a CTL in comparison to the reference peptide. Thus, when comparing the lytic activity in the linear portion of the effector:target curves with equimolar concentrations of the reference and substituted peptides, the observed percent specific killing of the target cells incubated with the substituted peptide should be equal to that of the reference peptide at an effector:target ratio that is no greater than 10-fold above the reference peptide effector:target ratio at which the comparison is being made.

Preferably, when the CTLs specific for a peptide of SEQ ID NO: 1-791 and 1514-1533 are tested against the substituted peptides, the peptide concentration at which the substituted peptides achieve half the maximal increase in lysis relative to background is no more than about 1 mM, preferably no more than about 1 μM, more preferably no more than about 1 nM, and still more preferably no more than about 100 pM, and most preferably no more than about 10 pM. It is also preferred that the substituted peptide be recognized by CTLs from more than one individual, at least two, and more preferably three individuals.

Thus, the epitopes of the present invention may be identical to naturally occurring tumor-associated or tumor-specific epitopes or may include epitopes that differ by no more than 4 residues from the reference peptide, as long as they have substantially identical antigenic activity.

It should be appreciated that an immunogen may consist only of a peptide of SEQ ID NO:1-791 or 1514-1533, or comprise a peptide of SEQ ID NO:1-791 or 1514-1533, or comprise a plurality of peptides selected from SEQ ID NO:1-791 and 1514-1533, or comprise a polypeptide that itself comprises one or more of the epitopic peptides of SEQ ID NO: 1-791 and 1514-1533.

The immunogenic peptides and polypeptides of the invention can be prepared synthetically, by recombinant DNA technology, or they can be isolated from natural sources such as tumor cells expressing the original protein product.

The polypeptides and oligopeptides disclosed herein can be synthesized in solution or on a solid support in accordance with conventional techniques. Various automated peptide synthesizers are commercially available and can be used in accordance with known protocols. See, for example, (Grant, G. A., Synthetic Peptides: A User's Guide, 1992, W. H. Freeman and Company, New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York). Fragments of polypeptides of the invention can also be synthesized as intermediates in the synthesis of a larger polypeptide.

Recombinant DNA technology may be employed wherein a nucleotide sequence which encodes an immunogenic peptide or polypeptide of interest is inserted into an expression vector, transformed or transfected into an appropriate host cell, and cultivated under conditions suitable for expression. These procedures are well known in the art to the skilled artisan, as described in (Coligan, J. E. et al, Current Protocols in Immunology, 1999, John Wiley & Sons, Inc., New York; Ausubel, F. M. et al, Current Protocols in Molecular Biology, 1999, John Wiley & Sons, Inc., New York; Molecular Cloning: A Laboratory Manual, 1989, Cold Spring Harbor Laboratory Press, Cold Spring Harbor). Thus, recombinantly produced peptides or polypeptides can be used as the immunogens of the invention.

The coding sequences for peptides of the length contemplated herein can be synthesized on commercially available automated DNA synthesizers using protocols that are well know in the art. See for example, (Grant, G. A., Synthetic Peptides: A User's Guide, 1992, W. H. Freeman and Company, New York; Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York). The coding sequences can also be modified such that a peptide or polypeptide will be produced that incorporates a desired amino acid substitution. The coding sequence can be provided with appropriate linkers, be ligated into suitable expression vectors that are commonly available in the art, and the resulting DNA or RNA molecule can be transformed or transfected into suitable hosts to produce the desired fusion protein. A number of such vectors and suitable host systems are available, and their selection is left to the skilled artisan. For expression of the fusion proteins, the coding sequence will be provided with operably linked start and stop codons, promoter and terminator regions, and a replication system to provide an expression vector for expression in the desired host cell. For example, promoter sequences compatible with bacterial hosts are provided in plasmids containing convenient restriction sites for insertion of the desired coding sequence. The resulting expression vectors are transformed into suitable bacterial hosts. Of course, yeast, insect, and mammalian host cells may also be used, employing suitable vectors and control sequences.

Host cells are genetically engineered (transduced or transformed or transfected) with the vectors of this invention which may be, for example, a cloning vector or an expression vector. The vector may be, for example, in the form of a plasmid, a viral particle, a phage, etc. The engineered host cells can be cultured in conventional nutrient media modified as appropriate for activating promoters, selecting transformants or amplifying the genes of the present invention. The culture conditions, such as temperature, pH and the like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan.

More particularly, the present invention also includes recombinant constructs comprising one or more of the sequences as broadly described above. The constructs comprise a vector, such as a plasmid or viral vector, into which a sequence of the invention has been inserted, in a forward or reverse orientation. In a preferred aspect of this embodiment, the construct further comprises regulatory sequences, including, for example, a promoter, operably linked to the sequence. Large numbers of suitable vectors and promoters are known to those of skill in the art, and are commercially available.

In a further embodiment, the present invention relates to host cells containing the above-described constructs. The host cell can be a higher eukaryotic cell, such as a mammalian cell, or a lower eukaryotic cell, such as a yeast cell, or the host cell can be a prokaryotic cell, such as a bacterial cell. Introduction of the construct into the host cell can be effected by calcium phosphate transfection, DEAE-Dextran mediated transfection, or electroporation (Ausubel, F. M. et al, Current Protocols in Molecular Biology, 1999, John Wiley & Sons, Inc., New York; Molecular Cloning: A Laboratory Manual, 1989, Cold Spring Harbor Laboratory Press, Cold Spring Harbor). Such cells can routinely be utilized for assaying CTL activity by having said genetically engineered, or recombinant, host cells express the immunogenic peptides of the present invention.

Various mammalian cell culture systems can also be employed to express recombinant protein. Examples of mammalian expression systems include the COS-7 lines of monkey kidney fibroblasts, described by Gluzman, Cell, 23:175 (1981), and other cell lines capable of expressing a compatible vector, for example, the C127, 3T3, CHO, HeLa and BHK cell lines. Mammalian expression vectors will comprise an origin of replication, a suitable promoter and enhancer, and also any necessary ribosome binding sites, polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5′ flanking non-transcribed sequences. DNA sequences derived from the SV40 splice, and polyadenylation sites may be used to provide the required nontranscribed genetic elements.

The polypeptide can be recovered and purified from recombinant cell cultures by methods including ammonium sulfate or ethanol precipitation, acid extraction, anion or cation exchange chromatography, phosphocellulose chromatography, hydrophobic interaction chromatography, affinity chromatography, hydroxylapatite chromatography and lectin chromatography. Protein refolding steps can be used, as necessary, in completing configuration of the mature protein. High performance liquid chromatography (HPLC) can be employed for final purification steps.

The immunogenic peptides of the present invention may be used to elicit CTLs ex vivo from either healthy individuals or from cancer patients with cancer, such as colorectal carcinoma, lung carcinoma, ovarian carcinoma, breast carcinoma, or prostate carcinoma. Such responses are induced by incubating in tissue culture the individual's CTL precursor lymphocytes together with a source of antigen presenting cells and the appropriate immunogenic peptide. Examples of suitable antigen presenting cells include dendritic cells, macrophages, and activated B cells. Typically, the peptide at concentrations between 10 and 40 μg/ml, would be pre-incubated with the antigen presenting cells for periods ranging from 1 to 18 hrs. β₂-microglobulin (4 μg/ml) can be added during this time period to enhance binding. The antigen presenting cells may also be held at room temperature during the incubation period (Ljunggren, H.-G. et al., Nature, 346:476-480, (1990)) or pretreated with acid (Zeh, H. J., III et al., Hum. Immunol., 39:79-86, (1994)) to promote the generation of denatured class I MHC molecules which can then bind the peptide. The precursor CTLs (responders) are then added to the antigen presenting cells to which the immunogenic peptide has bound (stimulators) at responder to stimulator ratios of between 5:1 and 50:1, and most typically between 10:1 and 20:1. The co-cultivation of the cells is carried out at 37° C. in RPMI 1640, 10% fetal bovine serum, 2 mM L-glutamine, and IL-2 (5-20 Units/ml). Other cytokines, such as IL-1, IL-7, and IL-12 may also be added to the culture. Fresh IL-2-containing media is added to the cultures every 2-4 days, typically by removing one-half the old media and replenishing it with an equal volume of fresh media. After 7-10 days, and every 7-10 days thereafter, the CTL are re-stimulated with antigen presenting cells to which immunogenic peptide has been bound as described above. Fresh IL-2-containing media is added to the cells throughout their culture as described above. Three to four rounds of stimulation, and sometimes as many five to eight rounds of stimulation, are required to generate a CTL response that can then be measured in vitro. The above described protocol is illustrative only and should not be considered limiting. Many in vitro CTL stimulation protocols have been described and the choice of which one to use is well within the knowledge of the skilled artisan. The peptide-specific CTL can be further expanded to large numbers by treatment with anti-CD3 antibody. For example, see (Riddell, S. R. and Greenberg, P. D., J. Immunol. Methods, 128:189-201, (1990); Walter, E. A. et al., N. Engl. J. Med., 333:1038-1044, (1995)).

Antigen presenting cells that are to be used to stimulate a CTL response are typically incubated with peptide of an optimal length, most commonly a nonapeptide, that allows for direct binding of the peptide to the class I MHC molecule without additional processing. Larger oligopeptides and polypeptides are generally ineffective in binding to class I MHC molecules as they are not efficiently processed into an appropriately sized peptide in the extracellular milieu. There a variety of approaches that are known in the art, however, that allow oligopeptides and polypeptides to be exogenously acquired by a cell, which then allows for their subsequent processing and presentation by a class I MHC molecule. Representative, but non-limiting examples of such approaches include electroporation of the molecules into the cell (Harding, C. H. III, Eur. J. Immunol., 22:1865-1869, (1992)), encapsulation of the molecules in liposomes which are fused to the cells of interest (Reddy, R. et al., J. Immunol. Methods, 141:157-163, (1991)), or osmotic shock in which the molecules are taken up via pinocytosis (Moore, M. W. et al., Cell, 54:777-785, (1988)). Thus, oligopeptides and polypeptides that comprise one or more of the peptides of the invention can be provided to antigen presenting cells in such a fashion that they are delivered to the cytoplasm of the cell, and are subsequently processed to allow presentation of the peptides.

Antigen presenting cells suitable for stimulating an in vitro CTL response that is specific for one or more of the peptides of the invention can also be prepared by introducing polynucleotide vectors encoding the sequences into the cells. These polynucleotides can be designed such that they express only a single peptide of the invention, multiple peptides of the invention, or even a plurality of peptides of the invention. There are a variety of approaches that are known in the art, that allow polynucleotides to be introduced and expressed in a cell, thus providing one or more peptides of the invention to the class I MHC molecule binding pathway. Representative, but non-limiting examples of such approaches include the introduction of plasmid DNA through particle-mediated gene transfer or electroporation (Tuting, T. et al., J. Immunol., 160:1139-1147, (1998)), or the transduction of cells with an adenovirus expressing the polynucleotide of interest (Perez-Diez, A. et al., Cancer Res., 58:5305-5309, (1998)). Thus, oligonucleotides that code for one or more of the peptides of the invention can be provided to antigen presenting cells in such a fashion that the peptides associate with class I MHC molecules and are presented on the surface of the antigen presenting cell, and consequently are available to stimulate a CTL response.

By preparing the stimulator cells used to generate an in vitro CTL response in different ways, it is possible to control the peptide specificity of CTL response. For example, the CTLs generated with a particular peptide will necessarily be specific for that peptide. Likewise, CTLs that are generated with a polypeptide or polynucleotide expressing or coding for particular peptides will be limited to specificities that recognize those peptides. More broadly, stimulator cells, and more specifically dendritic cells, can be incubated in the presence of the whole protein. As a further alternative, stimulator cells, and more specifically dendritic cells, can be transduced or transfected with RNA or DNA comprising the polynucleotide sequence encoding the protein. Under these alternative conditions, peptide epitopes that are naturally cleaved out of the protein, and which are generated in addition to peptide epitopes of SEQ ID NO:1-791 and 1514-1533 can associate with an appropriate class I MHC molecule, which may or may not include HLA-A1, -A2, or -A3. The selection of antigen presenting cells and the type of antigen with which to stimulate the CTL, is left to the ordinary skilled artisan.

In certain embodiments, the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing a molecule from A1, A2, or A3 supertypes (A11 is a member of the A3 supertype), whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has bound an immunogen comprising one or more of the peptides disclosed according to the invention.

In specific embodiments, the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing a molecule from A1, A2, or A3 supertypes, whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has exogenously acquired an immunogenic oligopeptide or polypeptide that comprises one or more of the peptides disclosed according to the invention.

A yet additional embodiment of the present invention is directed to a process for inducing a CTL response in vitro that is specific for a tumor cell expressing a molecule from A1, A2, or A3 supertypes, comprising contacting a CTL precursor lymphocyte with an antigen presenting cell that is expressing a polynucleotide coding for a polypeptide of the invention and wherein said polynucleotide is operably linked to a promoter.

In specific embodiments, the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing HLA-A1, HLA-A2, or HLA-A11, whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has bound an immunogen comprising one or more of the peptides disclosed according to the invention.

In specific embodiments, the methods of the present invention include a method for inducing a CTL response in vitro that is specific for a tumor cell expressing HLA-A1, HLA-A2, or HLA-A11, whereby the method comprises contacting a CTL precursor lymphocyte with an antigen presenting cell that has exogenously acquired an immunogenic oligopeptide or polypeptide that comprises one or more of the peptides disclosed according to the invention.

A yet additional embodiment of the present invention is directed to a process for inducing a CTL response in vitro that is specific for a tumor cell expressing HLA-A1, HLA-A2, or HLA-A11, comprising contacting a CTL precursor lymphocyte with an antigen presenting cell that is expressing a polynucleotide coding for a polypeptide of the invention and wherein said polynucleotide is operably linked to a promoter.

A variety of techniques exist for assaying the activity of CTL. These techniques include the labeling of target cells with radionuclides such as Na₂ ⁵¹Cr0₄ or ³H-thymidine, and measuring the release or retention of the radionuclides from the target cells as an index of cell death. Such assays are well-known in the art and their selection is left to the skilled artisan. Alternatively, CTL are known to release a variety of cytokines when they are stimulated by an appropriate target cell, such as a tumor cell expressing the relevant class I MHC molecule and the corresponding peptide. Non-limiting examples of such cytokines include IFN-γ, TNFα, and GM-CSF. Assays for these cytokines are well known in the art, and their selection is left to the skilled artisan. Methodology for measuring both target cell death and cytokine release as a measure of CTL reactivity are given in (Coligan, J. E. et al, Current Protocols in Immunology, 1999, John Wiley & Sons, Inc., New York).

After expansion of the antigen-specific CTLs, the latter are then adoptively transferred back into the patient, where they will destroy their specific target cell. The utility of such adoptive transfer is demonstrated in North, R. J. et al. (Infect. Immun., 67:2010-2012, (1999)) and Riddell, S. R. et al. (Science, 257:238-241, (1992)). In determining the amount of cells to reinfuse, the skilled physician will be guided by the total number of cells available, the activity of the CTL as measured in vitro, and the condition of the patient. Preferably, however, about 1×10⁶ to about 1×10¹², more preferably about 1×10⁸ to about 1×10¹¹, and even more preferably, about 1×10⁹ to about 1×10¹⁰ peptide-specific CTL are infused. Methodology for reinfusing the T cells into a patient are well known and exemplified in U.S. Pat. No. 4,844,893 to Honski, et al., and U.S. Pat. No. 4,690,915 to Rosenberg.

The peptide-specific CTL can be purified from the stimulator cells prior to infusion into the patient. For example, monoclonal antibodies directed towards the cell surface protein CD8, present on CTL, can be used in conjunction with a variety of isolation techniques such as antibody panning, flow cytometric sorting, and magnetic bead separation to purify the peptide-specific CTL away from any remaining non-peptide specific lymphocytes or from the stimulator cells. These methods are well known in the art, and are their selection is left to the skilled artisan. It should be appreciated that generation of peptide-specific CTL in this manner, obviates the need for stimulating the CTL in the presence of tumor. Thus, there is no chance of inadvertently reintroducing tumor cells into the patient.

Thus, one embodiment of the present invention relates to a process for treating a subject with cancer characterized by tumor cells expressing complexes of a molecule from A1, A2, or A3 supertypes, for example, HLA-A1, HLA-A2, or HLA-A11, whereby CTLs produced in vitro according to the present invention are administered in an amount sufficient to destroy the tumor cells through direct lysis or to effect the destruction of the tumor cells indirectly through the elaboration of cytokines.

Another embodiment of the present invention is directed to a process for treating a subject with cancer characterized by tumor cells expressing any class I MHC molecule and an epitope of SEQ ID NO: 1-791 and 1514-1533, whereby the CTLs are produced in vitro and are specific for the epitope or original protein and are administered in an amount sufficient to destroy the tumor cells through direct lysis or to effect the destruction of the tumor cells indirectly through the elaboration of cytokines.

In the foregoing embodiments the cancer to be treated may include a colorectal carcinoma, an ovarian carcinoma, a breast carcinoma, a lung carcinoma, and prostate carcinoma, but especially ovarian carcinoma.

The ex vivo generated CTL can be used to identify and isolate the T cell receptor molecules specific for the peptide. The genes encoding the alpha and beta chains of the T cell receptor can be cloned into an expression vector system and transferred and expressed in naive T cells from peripheral blood, T cells from lymph nodes, or T lymphocyte progenitor cells from bone marrow. These T cells, which would then be expressing a peptide-specific T cell receptor, would then have anti-tumor reactivity and could be used in adoptive therapy of cancer, and more specifically cancer, colorectal carcinoma, ovarian carcinoma, breast carcinoma, lung carcinoma, and prostate carcinoma.

In addition to their use for therapeutic or prophylactic purposes, the immunogenic peptides of the present invention are useful as screening and diagnostic agents. Thus, the immunogenic peptides of the present invention, together with modern techniques of gene screening, make it possible to screen patients for the presence of genes encoding such peptides on cells obtained by biopsy of tumors detected in such patients. The results of such screening may help determine the efficacy of proceeding with the regimen of treatment disclosed herein using the immunogens of the present invention.

Alternatively, the immunogenic peptides disclosed herein, as well as functionally similar homologs thereof, may be used to screen a sample for the presence of CTLs that specifically recognize the corresponding epitopes. The lymphocytes to be screened in this assay will normally be obtained from the peripheral blood, but lymphocytes can be obtained from other sources, including lymph nodes, spleen, tumors, and pleural fluid. The peptides of the present invention may then be used as a diagnostic tool to evaluate the efficacy of the immunotherapeutic treatments disclosed herein. Thus, the in vitro generation of CTL as described above would be used to determine if patients are likely to respond to the peptide in vivo. Similarly, the in vitro generation of CTL could be done with samples of lymphocytes obtained from the patient before and after treatment with the peptides. Successful generation of CTL in vivo should then be recognized by a correspondingly easier ability to generate peptide-specific CTL in vitro from lymphocytes obtained following treatment in comparison to those obtained before treatment.

The oligopeptides of the invention, such as SEQ ID NO: 1-791 and 1514-1533, can also be used to prepare class I MHC tetramers which can be used in conjunction with flow cytometry to quantitate the frequency of peptide-specific CTL that are present in a sample of lymphocytes from an individual. Specifically, for example, class I MHC molecules comprising peptides of SEQ ID NO: 1-791 and 1514-1533, would be combined to form tetramers as exemplified in U.S. Pat. No. 5,635,363. Said tetramers would find use in monitoring the frequency of CTLs in the peripheral blood, lymph nodes, or tumor mass of an individual undergoing immunotherapy with the peptides, proteins, or polynucleotides of the invention, and it would be expected that successful immunization would lead to an increase in the frequency of the peptide-specific CTL.

As stated above, a vaccine in accordance with the present invention may include one or more of the hereinabove described polypeptides or active fragments thereof, or a composition, or pool, of immunogenic peptides disclosed herein. When employing more than one polypeptide or active fragment, two or more polypeptides and/or active fragments may be used as a physical mixture or as a fusion of two or more polypeptides or active fragments. The fusion fragment or fusion polypeptide may be produced, for example, by recombinant techniques or by the use of appropriate linkers for fusing previously prepared polypeptides or active fragments.

The immunogenic molecules of the invention, including vaccine compositions, may be utilized according to the present invention for purposes of preventing, suppressing or treating diseases causing the expression of the immunogenic peptides disclosed herein, such as where the antigen is being expressed by tumor cells. As used in accordance with the present invention, the term “prevention” relates to a process of prophylaxis in which an animal, especially a mammal, and most especially a human, is exposed to an immunogen of the present invention prior to the induction or onset of the disease process. This could be done where an individual has a genetic pedigree indicating a predisposition toward occurrence of the disease condition to be prevented. For example, this might be true of an individual whose ancestors show a predisposition toward certain types of cancer. Alternatively, the immunogen could be administered to the general population as is frequently done for infectious diseases. Alternatively, the term “suppression” is often used to describe a condition wherein the disease process has already begun but obvious symptoms of said condition have yet to be realized. Thus, the cells of an individual may have become cancerous but no outside signs of the disease have yet been clinically recognized. In either case, the term prophylaxis can be applied to encompass both prevention and suppression. Conversely, the term “treatment” is often utilized to mean the clinical application of agents to combat an already existing condition whose clinical presentation has already been realized in a patient. This would occur where an individual has already been diagnosed as having a tumor.

It is understood that the suitable dosage of an immunogen of the present invention will depend upon the age, sex, health, and weight of the recipient, the kind of concurrent treatment, if any, the frequency of treatment, and the nature of the effect desired. However, the most preferred dosage can be tailored to the individual subject, as determined by the researcher or clinician. The total dose required for any given treatment will commonly be determined with respect to a standard reference dose as set by a manufacturer, such as is commonly done with vaccines, such dose being administered either in a single treatment or in a series of doses, the success of which will depend on the production of a desired immunological result (i.e., successful production of a CTL-mediated response to the antigen, which response gives rise to the prevention and/or treatment desired). Thus, the overall administration schedule must be considered in determining the success of a course of treatment and not whether a single dose, given in isolation, would or would not produce the desired immunologically therapeutic result or effect.

The therapeutically effective amount of a composition containing one or more of the immunogens of this invention, is an amount sufficient to induce an effective CTL response to the antigen and to cure or arrest disease progression. Thus, this dose will depend, among other things, on the identity of the immunogens used, the nature of the disease condition, the severity of the disease condition, the extent of any need to prevent such a condition where it has not already been detected, the manner of administration dictated by the situation requiring such administration, the weight and state of health of the individual receiving such administration, and the sound judgment of the clinician or researcher. Thus, for purposes of prophylactic or therapeutic administration, effective amounts would generally lie within the range of from 1.0 μg to about 5,000 μg of peptide for a 70 kg patient, followed by boosting dosages of from about 1.0 μg to about 1,000 μg of peptide pursuant to a boosting regimen over days, weeks or even months, depending on the recipient's response and as necessitated by subsequent monitoring of CTL-mediated activity within the bloodstream. Of course, such dosages are to be considered only a general guide and, in a given situation, may greatly exceed such suggested dosage regimens where the clinician believes that the recipient's condition warrants more a aggressive administration schedule. Needless to say, the efficacy of administering additional doses, and of increasing or decreasing the interval, may be re-evaluated on a continuing basis, in view of the recipient's immunocompetence (for example, the level of CTL activity with respect to tumor-associated or tumor-specific antigens).

For such purposes, the immunogenic compositions according to the present invention may be used against a disease condition such as cancer by administration to an individual by a variety of routes. The composition may be administered parenterally or orally, and, if parenterally, either systemically or topically. Parenteral routes include subcutaneous, intravenous, intradermal, intramuscular, intraperitoneal, intranasal, transdermal, or buccal routes. One or more such routes may be employed. Parenteral administration can be, for example, by bolus injection or by gradual perfusion over time.

Generally, vaccines are prepared as injectables, in the form of aqueous solutions or suspensions. Vaccines in an oil base are also well known such as for inhaling. Solid forms which are dissolved or suspended prior to use may also be formulated. Pharmaceutical carriers, diluents and excipients are generally added that are compatible with the active ingredients and acceptable for pharmaceutical use. Examples of such carriers include, but are not limited to, water, saline solutions, dextrose, or glycerol. Combinations of carriers may also be used. These compositions may be sterilized by conventional, well known sterilization techniques including sterile filtration. The resulting solutions may be packaged for use as is, or the aqueous solutions may be lyophilized, the lyophilized preparation being combined with sterile water before administration. Vaccine compositions may further incorporate additional substances to stabilize pH, or to function as adjuvants, wetting agents, or emulsifying agents, which can serve to improve the effectiveness of the vaccine.

The concentration of the CTL stimulatory peptides of the invention in pharmaceutical formulations are subject to wide variation, including anywhere from less than 0.01% by weight to as much as 50% or more. Factors such as volume and viscosity of the resulting composition must also be considered. The solvents, or diluents, used for such compositions include water, possibly PBS (phosphate buffered saline), or saline itself, or other possible carriers or excipients.

The immunogens of the present invention may also be contained in artificially created structures such as liposomes, ISCOMS, slow-releasing particles, and other vehicles which increase the immunogenicity and/or half-life of the peptides or polypeptides in serum. Liposomes include emulsions, foams, micelies, insoluble monolayers, liquid crystals, phospholipid dispersions, lamellar layers and the like. Liposomes for use in the invention are formed from standard vesicle-forming lipids which generally include neutral and negatively charged phospholipids and a sterol, such as cholesterol. The selection of lipids is generally determined by considerations such as liposome size and stability in the blood. A variety of methods are available for preparing liposomes as reviewed, for example, by (Coligan, J. E. et al, Current Protocols in Protein Science, 1999, John Wiley & Sons, Inc., New York) and see also U.S. Pat. Nos. 4,235,871, 4,501,728, 4,837,028, and 5,019,369.

Liposomes containing the peptides or polypeptides of the invention can be directed to the site of lymphoid cells where the liposomes then deliver the selected immunogens directly to antigen presenting cells. Targeting can be achieved by incorporating additional molecules such as proteins or polysaccharides into the outer membranes of said structures, thus resulting in the delivery of the structures to particular areas of the body, or to particular cells within a given organ or tissue. Such targeting molecules may a molecule that binds to receptor on antigen presenting cells. For example an antibody that binds to CD80 could be used to direct liposomes to dendritic cells.

The immunogens of the present invention may also be administered as solid compositions. Conventional nontoxic solid carriers including pharmaceutical grades of mannitol, lactose, starch, magnesium, cellulose, glucose, sucrose, sodium saccharin, and the like. Such solid compositions will often be administered orally, whereby a pharmaceutically acceptable nontoxic composition is formed by incorporating the peptides and polypeptides of the invention with any of the carriers listed above. Generally, such compositions will contain 10-95% active ingredient, and more preferably 25-75% active ingredient.

Aerosol administration is also an alternative, requiring only that the immunogens be properly dispersed within the aerosol propellant. Typical percentages of the peptides or polypeptides of the invention are 0.01%-20% by weight, preferably 1%-10%. The use of a surfactant to properly disperse the immunogen may be required. Representative surfactants include the esters or partial esters of fatty acids containing from 6 to 22 carbon atoms, such as caproic, octanoic, lauric, palmitic, stearic, linoleic, linolenic, olesteric and oleic acids with an aliphatic polyhydric alcohol or its cyclic anhydride. Mixed esters, such as mixed or natural glycerides may be employed. The surfactant may constitute 0.1-20% by weight of the composition, preferably 0.25-5%. Typical propellants for such administration may include esters and similar chemicals but are by no means limited to these. A carrier, such as lecithin for intranasal delivery, may also be included.

The peptides and polypeptides of the invention may also be delivered with an adjuvant. Adjuvants include, but are not limited to complete or incomplete Freund's adjuvant, Montanide ISA-51, Lymphocyte Activation Gene-3 (LAG-)3, aluminum phosphate, aluminum hydroxide, alum, and saponin. Adjuvant effects can also be obtained by injecting a variety of cytokines along with the immunogens of the invention. These cytokines include, but are not limited to IL-1, IL-2, IL-7, IL-12, and GM-CSF.

The peptides and polypeptides of the invention can also be added to professional antigen presenting cells such as dendritic cells that have been prepared ex vivo. For example, the dendritic cells could be prepared from CD34 positive stem cells from the bone marrow, or they could be prepared from CD14 positive monocytes obtained from the peripheral blood. The dendritic cells are generated ex vivo using cytokines such as GM-CSF, IL-3, IL-4, TNF, and SCF. The cultured DC are then pulsed with peptides at various concentrations using standard methods that are well known in the art. The peptide-pulsed dendritic cells can then be administered either intraveneously, subcutaneously, or intradermally, and the immunization may also include cytokines such as IL-2 or IL-12.

The present invention is also directed to a vaccine in which an immunogen of the present invention is delivered or administered in the form of a polynucleotide encoding the a polypeptide or active fragment as disclosed herein, whereby the peptide or polypeptide or active fragment is produced in vivo. The polynucleotide may be included in a suitable expression vector and combined with a pharmaceutically acceptable carrier. For example, the peptides or polypeptides could be expressed in plasmid DNA and nonreplicative viral vectors such as vaccinia, fowlpox, Venezuelan equine encephalitis virus, adenovirus, or other RNA or DNA viruses. These examples are meant to be illustrative only and should not be viewed as self-limiting A wide variety of other vectors are available and are apparent to those skilled in the art from the description given herein. In this approach, a portion of the nucleotide sequence of the viral vector is engineered to express the peptides or polypeptides of the invention. Vaccinia vectors and methods useful in immunization protocols are described in U.S. Pat. No. 4,722,848, the disclosure of which is incorporated herein by reference in its entirety.

Regardless of the nature of the composition given, additional therapeutic agents may also accompany the immunogens of the present invention. Thus, for purposes of treating tumors, compositions containing the immunogens disclosed herein may, in addition, contain other antitumor pharmaceuticals. The use of such compositions with multiple active ingredients is left to the discretion of the clinician.

In addition, the immunogens of the present invention can be used to stimulate the production of antibodies for use in passive immunotherapy, for use as diagnostic reagents, and for use as reagents in other processes such as affinity chromatography.

The present invention also relates to antibodies that react with immunogens, such as a polypeptide comprising one or more of the epitopic peptides of SEQ ID NO: 1-791 and 1514-1533 as disclosed herein. Active fragments of such antibodies are also specifically contemplated. Such antibodies, and active fragments of such antibodies, for example, and Fab structure, may react with, including where it is highly selective or specific for, an immunogenic structure comprising 2, 3, 4 or more of the epitopic peptides of the invention.

With the advent of methods of molecular biology and recombinant technology, it is now possible to produce antibody molecules by recombinant means and thereby generate gene sequences that code for specific amino acid sequences found in the polypeptide structure of the antibodies. Such antibodies can be produced by either cloning the gene sequences encoding the polypeptide chains of said antibodies or by direct synthesis of said polypeptide chains, with in vitro assembly of the synthesized chains to form active tetrameric (H₂L₂) structures with affinity for specific epitopes and antigenic determinants. This has permitted the ready production of antibodies having sequences characteristic of neutralizing antibodies from different species and sources.

Regardless of the source of the antibodies, or how they are recombinantly constructed, or how they are synthesized, in vitro or in vivo, using transgenic animals, such as cows, goats and sheep, using large cell cultures of laboratory or commercial size, in bioreactors or by direct chemical synthesis employing no living organisms at any stage of the process, all antibodies have a similar overall 3 dimensional structure. This structure is often given as H2L2 and refers to the fact that antibodies commonly comprise 2 light (L) amino acid chains and 2 heavy (H) amino acid chains. Both chains have regions capable of interacting with a structurally complementary antigenic target. The regions interacting with the target are referred to as “variable” or “V” regions and are characterized by differences in amino acid sequence from antibodies of different antigenic specificity.

The variable regions of either H or L chains contains the amino acid sequences capable of specifically binding to antigenic targets. Within these sequences are smaller sequences dubbed “hypervariable” because of their extreme variability between antibodies of differing specificity. Such hypervariable regions are also referred to as “complementarity determining regions” or “CDR” regions. These CDR regions account for the basic specificity of the antibody for a particular antigenic determinant structure.

The CDRs represent non-contiguous stretches of amino acids within the variable regions but, regardless of species, the positional locations of these critical amino acid sequences within the variable heavy and light chain regions have been found to have similar locations within the amino acid sequences of the variable chains. The variable heavy and light chains of all antibodies each have 3 CDR regions, each non-contiguous with the others (termed L1, L2, L3, H1, H2, H3) for the respective light (L) and heavy (H) chains. The accepted CDR regions have been described in the text and figures of Kabat et al. (J. Biol. Chem. 252:6609-6616 (1977)).

In all mammalian species, antibody polypeptides contain constant (i.e., highly conserved) and variable regions, and, within the latter, there are the CDRs and the so-called “framework regions” made up of amino acid sequences within the variable region of the heavy or light chain but outside the CDRs.

The antibodies disclosed according to the invention may also be wholly synthetic, wherein the polypeptide chains of the antibodies are synthesized and, possibly, optimized for binding to the polypeptides disclosed herein as being receptors. Such antibodies may be chimeric or humanized antibodies and may be fully tetrameric in structure, or may be dimeric and comprise only a single heavy and a single light chain. Such antibodies may also include fragments, such as Fab and F(ab₂)′ fragments, capable of reacting with and binding to any of the polypeptides disclosed herein as being receptors.

A further embodiment of the present invention relates to a method for inducing a CTL response in a subject comprising administering to subjects that express HLA-A1 antigens an effective (i.e., CTL-stimulating amount) of an immunogen of the invention that does not comprise the entire protein expressing the epitopic peptides disclosed herein (i.e., one that comprises less than the entire protein where the protein is a naturally occurring polypeptide) in an amount sufficient to induce a CTL response to tumor cells expressing at least HLA-A1 or HLA-A2, as the case may be, thereby eliciting a cellular response against said tumor cells.

A still further embodiment of the present invention relates to a method for inducing a CTL response in a subject, wherein the immunogen is in the form of a polynucleotide. In one non-limiting example, the method comprises administering to subjects that express HLA-A1 at least one CTL epitope, wherein said epitope or epitopes are selected from a group comprising the peptides disclosed according to the invention, and are coded within a polynucleotide sequence that does not comprise the entire protein coding region, in an amount sufficient to induce a CTL response to tumor cells expressing HLA-A1 or HLA-A2.

While the below examples are provided to illustrate the invention, it is to be understood that these methods and examples in no way limit the invention to the embodiments described herein and that other embodiments and uses will no doubt suggest themselves to those skilled in the art. All publications, patents, and patent applications cited herein are hereby incorporated by reference, as are the references cited therein. It is also to be understood that throughout this disclosure where the singular is used, the plural may be inferred and vice versa and use of either is not to be considered limiting.

EXAMPLE 1

Cell Lines

For HLA-A1 and HLA-A11 studies, ARGOV57, a HLA-A1/11 positive ovarian cell line, was established by culturing tumor cells from an ascitic fluid from an ovarian patient.

For HLA-A2 studies, OVCAR3, a HLA-A2 positive ovarian carcinoma cell line, was established by culturing tumor cells from an ascitic fluid from an ovarian patient.

SKOV3-A2, a HLA-A2 stably expressing ovarian carcinoma cell line, was established by culturing tumor cells from an ascitic fluid from an ovarian patient and transduced with HLA-A2 gene.

EXAMPLE 2

Immunoaffinity Purification

ARGOV57 cells were grown in 10-chamber Nunc cell factories (Fisher, Pittsburgh, Pa.). The cells were harvested by treatment with 0.45% trypsin and 0.32 mM EDTA, washed two times in phosphate-buffered saline solution (pH 7.4), and stored as cell pellets at −80° C. Aliquots of 6-8×10¹⁰ cells were solubilized at 5-10×10⁶ cells/ml in 20 mM Tris, pH 8.0, 150 mM NaCl, 1% CHAPS, 18.5 μg/ml iodoacetamide, 5 μg/ml aprotonin, 10 μg/ml leupeptin, 10 μg/ml pepstatin A, 5 mM EDTA, 0.2% sodium azide, and 17.4 μg/ml phenylmethylsulfonyl fluoride for 1 h. This and all subsequent steps were performed with ice-cold solutions and at 4° C. The lysates were then centrifuged at 100,000×g, the pellets discarded, and the supernatants passed through a 0.22 μm filter. The supernatants were then passed over a series of columns with the first containing Sepharose, and the second containing the HLA-A1-specific monoclonal antibody, GAP-A1, bound to a protein A-Sepharose matrix. The second column was then sequentially washed with 20 column volumes of 20 mM Tris, pH 8.0, 150 mM NaCl, 20 column volumes of 20 mM Tris, pH 8.0, 1.0 M NaCl, and 20 column volumes of 20 mM Tris, pH 8.0. The peptides were eluted from the column with 5 column volumes of 10% acetic acid. The isolated HLA-A1 molecules were then boiled for 5 min to further dissociate any bound peptide from the heavy chains. The peptides were then separated from the co-purifying class I heavy chain and β₂-microglobulin by centrifugation on a Ultrafree-CL membrane with a nominal molecular weight cut-off of 5,000 Daltons (Millipore, Bedford, Mass.).

For a separate study, OVCAR3 or SKOV3 cells were successfully prepared using the same procedure as just described except that HLA-A2 molecules were prepared using HLA-A2 specific antibodies.

EXAMPLE 3

Peptide Fractionation

The peptide extracts were fractionated by RP-HPLC (Reversed Phase-High Performance Liquid Chromatography) using an Applied Biosystems (ABI) model 140B system. The extracts were concentrated by vacuum centrifugation from about 20 ml down to 250 μl and injected into either a Brownlee (Norwalk, Conn.) C₁₈ Aquapore column (2.1 mm×3 cm; 300 Å; 7 μm) or a Higgins (Mountain View, Calif.) C18 Haisil column (2.1 mm×4 cm; 300 Å; 5 μm). The peptides were eluted by first using a gradient of acetonitrile/0.085% TFA (trifluoroacetic acid) in 0.1% TFA/water, with the concentration of acetonitrile increasing from 0-9% (0-5 minutes), 9-36% (5-55 minutes), and 36-60% (55-62 minutes). A second dimension fractionation of combined fractions 17 and 18 from the first dimension (TFA) fraction was accomplished using the same gradient but with the substitution of HFBA (heptafluorobutyric acid) for TFA. The flow rate was 200 μl/min, and fractions were collected at 1 min (Brownlee column) or 40 second (Higgins column) intervals. A third dimension of RP-HPLC was achieved using an Eldex (Napa, Calif.) MicroPro Pump, a homemade C₁₈ microcapillary column, and an ABI model 785A UV absorbance detector. The column was prepared by packing a 27 cm bed of 10 μm C₁₈ particles in a section of 285 μm o.d./75 μm i.d. fused silica (Polymicro Technologies, Phoenix, Ariz.). Peptides in combined fractions 26 and 27 of the second dimension fraction were loaded onto this column and eluted with a gradient of acetonitrile/0.67% triethylamine acetate/water in 0.1% triethylamine acetate/water, with the concentration of acetonitrile increasing from 0-60% in 40 minutes. The flow rate was about 300 nl/min, and fractions were collected into 25 μl of water every 30 s. In all RP-HPLC experiments, peptides were detected by monitoring UV absorbance at 214 nm.

EXAMPLE 4

Mass Spectrometric Analysis

The second dimension HPLC fraction was analyzed using an affluent splitter on the microcapillary HPLC column. In this experiment, the column (360 μm o.d.×100 μm i.d. with a 25 cm C₁₈ bed) was butt connected with a zero dead volume tee (Valco, Houston, Tex.) to two pieces of fused silica of different lengths (25 μm and 40 μm i.d.). Peptides were eluted with a 34 min gradient of 0-60% acetonitrile. The 25 m capillary deposited one-fifth of the HPLC effluent into the wells of a microtiter plate for use in CTL epitope reconstitution assays, whereas the remaining four-fifths of the effluent was directed into the mass spectrometer. Ions were formed by electrospray ionization, and mass spectra were recorded by scanning between mass to charge ratios (m/z) 300 and 1400 every 1.5 seconds. Peptide sequences were determined by CAD (collision-activated dissociation) tandem mass spectrometry as described in the literature (Hunt, D. F. et al., Proc. Natl. Acad. Sci. U.S.A, 83:6233-6237, (1986)).

EXAMPLE 5

Homology Searches of Identified Peptide Sequences

Proteins containing peptides corresponding to the masses identified by MS were analyzed with the search algorithm, SEQUEST. Searches were also carried out on the GenBank non-redundant sequence database (http:/ncbi,nlm.nih.gov/Entrez/) as well as on our own unique database of 2943 specific sequences compiled from GenBank and EST data-base entries. Upon experimental confirmation of the peptide Sequence, a tBLASTn search of the GenBank non redundant databaxe was performed to identify any genes containing the DNA sequence encoding the peptice.

EXAMPLE 6

Peptide Synthesis

Peptides were synthesized using a Gilson (Madison, Wis.) AMS 422 multiple peptide synthesizer. Quantities of 10 μMol were synthesized using conventional FMOC amino acids, resins, and chemical techniques. Peptides were purified by RP-HPLC using a 4.6 mm×100 mm POROS (Perseptive Biosystems, Cambridge, Mass.) column and a 10 min, 0-60% acetonitrile in 0.1% TFA gradient.

EXAMPLE 7

Generation of Monocyte-Derived DC and Peptide Loading

PBMC were purified from HLA-A2⁺ normal donor blood using lymphocyte separation media (Cappel ICN Biomedical, Aurora, Ohio). PBMC (5.3×10⁶) were added to individual wells of a 24-well cluster plate (Costar, Corning, N.Y.) in 1.0 ml of serum-free AIM-V medium (Life Technologies) and allowed to adhere for 60 min at 37° C. Non-adherent cells were removed and saved as a source of effector T cells. Adherent PBMC (˜8.3×10⁵/well) were then pulsed with 50 mg/ml synthetic peptides in serum-free AIM-V medium containing 1.5 mg/ml β₂-microg lobulin (Calbiochem-Novabiochem, San Diego, Calif.) and incubated for 2 h at 37° C. Unbound peptides were aspirated and the wells washed with media.

Monocyte-derived DC were generated as follows. PBMC (5.3×10⁷) were allowed to adhere in T-75 flasks (Corning) in 10 ml of serum-free AIM-V medium for 60 min at 37° C. Non-adherent cells were collected as a source of effector T cells and pooled with the previous collection above. Adherent monocytes in flasks were then exposed to recombinant human granulocyte macrophage colony stimulating factor (GM-CSF, 25 ng/ml; Peprotech) and recombinant human IL-4 (100 ng/ml; Peprotech) in 10 ml of AIM-V medium containing 10% heat-inactivated FBS. DC obtained by this method [immature DC (iDC)] are characterized by expression of low levels of CD83, CD80, CD86, and HLA class I and class II molecules (data not shown).

Mature DC (mDC) were obtained by exposing day 5 DC cultures to recombinant soluble CD40 ligand (sCD40L; Peprotech) at 1.5 mg/ml for 24 h in the presence of 25 ng/ml GM-CSF and are characterized by expression of high levels of CD80, CD86, and HLA class I and class II molecules. mDC were harvested, washed, pulsed with 5 mg/ml peptide in serum-free AIM-V medium and irradiated (5000 rad) prior to use as stimulators.

EXAMPLE 8

Generation of Peptide-Specific CTL

The protocol used here is a modification of the method described by Plebanski et al. (Eur. J. Immunol. 25:1783, (1995)). CTL to peptide were generated by 3±4 cycles of stimulation with peptide-loaded APC. For the first round of stimulation (day 0), T cells or non-adherent PBMC from above (2.3×10⁶/ml or 4.3×10⁶ per well) were added in bulk (CD4⁺, CD8⁺, NK, etc.) to adherent PBMC-loaded peptides in serum-free medium (50 mg/ml), β₂-microglobulin (1.5 mg/ml) (Calbiochem-Novabiochem), recombinant human IL-7 (5 ng/ml) (Peprotech) and keyhole limpet hemocyanin (5 mg/ml) (Sigma, St Louis, Mo.). Cultures were re-stimulated with iDC every 7 days, pulsed with varying amounts of peptide (second round 25 mg/ml, third round 10 mg/ml) and irradiated (5000 rad) on day 8. At each re-stimulation, the T cells were transferred to new plates by first aspirating 70% of spent media in wells and then transferring the pooled contents to a new plate. Fresh IL-7 was added at each re-stimulation. The responder:stimulator (T cell:DC) ratio was set at 20 for each stimulation. Recombinant human IL-2 (10 U/ml) was added on day 5 after each re-stimulation.

Prior to ⁵¹Cr-release assay, the T cells were harvested and CD8⁺ T cells were purified by positive selection using CD8⁺ microbeads immunomagnetic cell separation with MACS kit (Miltenyi Biotec, Auburn, Calif.). If a fourth round of stimulation was necessary following CTL analysis, the CTL were pulsed as before, except with 5±10 mg/ml of peptide.

EXAMPLE 9

Generation of Allospecific CTL

HLA-A2-allospecific CTL were obtained in a mixed lymphocyte reaction by repeated stimulation of HLA-A3⁺ PBMC (responders) with irradiated HLA-A2⁺ stimulator PBMC at a ratio of 10:1 in the presence of 10 U/ml IL-2. Stimulation was repeated weekly with PBMC from different HLA-A2⁺ donors so as to minimize alloresponse to non-HLA-A2 antigens. T cells were assessed for lysis on several HLA-A2⁺ targets including tumor cells, EBV-B cells and HLA-A3⁺ targets every week after the third round of stimulation.

EXAMPLE 10

CTL Expansion

Expansion of large numbers of peptide-specific or HLA-A2-allospecific CTL was achieved by culturing 5.3×10⁴±1.3×10⁵ T cells around day 6 or 7 post peptide- or allostimulation in the presence of 2.5-3.0×10⁷ irradiated (5000 rad) allogeneic normal donor PBMC coated with anti-CD3 antibody at 10 ng/ml (BD PharMingen, San Diego, Calif.) and 25 U/ml of recombinant human IL-2 (Peprotech) in a final volume of 30 ml RPMI medium. Media changes with IL-2 addition (50 U/ml) were effected on days 5 and 8. Cells were harvested for cytotoxicity assays on days 10±12 and re-stimulated or frozen for later use.

EXAMPLE 11

⁵¹Cr-Release Cytotoxicity Assay

The standard 4-h Cr-release assay was performed in 96-well V-bottomed microplates. Target cells in suspension (T2, C1R.A2, B-LCL and K562) were labeled with 100 mCi Na₂ ⁵¹CrO4 (NEN Life Science, Boston, Mass.) per 1.3×10⁶ cells either overnight (˜6±18 h) in 5 ml RPMI 1640 media containing 2±5% FBS or for 60±90 min at 37° C. directly with the cell pellet in the case of adherent cells (tumor cell lines and control lines). Labeling was terminated by washing the targets with cold media containing 5% FBS for a total of three washes. Target cells were resuspended at a concentration of 2-3×10⁴/ml. About 2-3×10³ targets in 100 ml were delivered to each well containing CTL (effectors) seeded at different E:T ratios. Spontaneous release wells contained targets in media alone, while maximal release wells contained targets in 2% NP-40 detergent (Igepal CA-630; Sigma). HLA restriction of CTL-mediated killing was achieved by preincubation of targets with HLA-specific antibodies prior to incubation with CTL.

The plate was gently spun for 1±2 min and incubated at 37° C. for 4 h. For harvesting assay plates, 100 ml of supernatants from the wells was transferred to counting tubes (USA Scientific) and g counts were determined in a g counter (ICN Micromedic Systems, Huntsville, Ala.). Cytolytic activity of T cells was expressed in percent specific lysis as follows: specific lysis={[experimental release (c.p.m.)±spontaneous release (c.p.m.)]/[maximal release (c.p.m.)±spontaneous release (c.p.m.)]}.

EXAMPLE 12

Competitive Inhibition Assay

Peptide-stimulated CTL were reacted with ⁵¹Cr-labeled Ov2 tumor cells (E:T ratio of 40) in the presence of excess of cold targets in a 4-h Cr-release assay. Cold targets were either empty T2 cells, T2 cells pulsed with 1 mg/ml relevant peptide (used to stimulate CTL) or irrelevant (control) peptides (HER-2/neu 369±377 or MART 127±35), or IFN-γ pre-treated tumor cells (SKOV3.A2 and OVCAR 3) with the cold target in 5-fold excess of the hot target. Results indicate that (i) CTL show specific interaction with the peptide to which they are sensitized to, and (ii) CTL compete for similar epitopes presented on Ov2 as were found in SKOV3.A2 and OVCAR3 cell lines by MS.

TABLE 2 Description of Fragments, Parent Sequence Iden- tification and Parent SwissProt Identification Number for peptides 1-791 and 1514-1533 Parent Swiss- Prot SEQ Identi- ID Parent Sequence fication NO: Fragment Identification No. 1 AEAEFYRQV BCL-6 corepressor long Q6W2J9 2 IYNGDMEKI isoform_E1B_19K/Bcl-2- Q12983 interacting protein Nip3 3 KEFDGKSLV Similar to Heat shock P08238 protein HSP 90-beta (HSP 84) (HSP 90) 4 HIPAGTLVQV Cytochrome P450 11B2, P19099 mitochondrial precursor 5 SLAEGLRTV 2′-5′oligoadenylate Q2HJ14 synthetase 3 6 YLGDGPKLV 26S protease regulatory P62191 subunit 4 (P26s4) 7 YLASLIRSV 26S proteasome non- P51665 ATPase regulatory subunit 7 8 FVDDYTVRV 26S proteasome non- O00487 ATPase regulatory subunit 14 9 KLLEPVLLL 40S ribosomal protein P62249 S16 10 KLIEVDDERKL 40S ribosomal protein P62753 S6 (Phosphoprotein NP33) 11 RLFEGNALL 40S ribosomal protein P46781 S9 12 TLYEAVREV 60S ribosomal protein P62906 L10a (CSA-19) 13 NMVAKVDEV 60S ribosomal protein P62906 L10a (CSA-19) 14 SLIKQIPRI 60S ribosomal protein P62906 L10a (CSA-19) 15 FLSEEGGHVAV 6-phosphofructo-2- Q16877 kinase/fructose-2,6- biphosphatase 4 (6PF-2- K/Fru-2,6-P2ASE testis- type isozyme) 16 IETINFHEV Cleavage and polyadeny- Q9UKF6 lation specificity factor, 73 kDa subunit (CPSF 73 kDa subunit) 17 YLNDLIHSV A kinase anchor protein O43572 10, mitochondrial precursor 18 RVAPEEHPVL Actin, cytoplasmic 1 P60709 (Beta-actin) 19 DVLKIPVQLV Activated T-cell marker Q6YHK3 CD109 20 LSDFLKANV Activin receptor type P27037 2A precursor (EC 2.7.11.30) 21 DLCFEKVNV ADAM19 protein Q8TBU7 22 KLHDINAQL AP-1 complex subunit Q10567 beta-1 (Adapter-related protein complex 1 beta- 1 subunit) (Beta- adaptin 1) 23 GNGAPDVFQT Adaptor-related protein Q9BYI8 NF01019537 24 IDAIRIPVL Lung alpha/beta hydro- Q96SE0 lase protein 1 25 FIASKGVKLV Alpha-actinin-3 Q08043 26 HRPDLIDY Alpha-actinin-3 Q08043 27 SPQGLELALPS Ankyrin-2 (Brain Q01484 ankyrin) (Ankyrin-B) 28 KIVKRPSLQFL Ankyrin repeat and SOCS Q8WXJ9 box protein 17 29 TLVTVSAAKT Anti-colorectal carcin- Q65ZQ1 oma heavy chain 30 KVLDGSPIEV APOBEC1 complementation Q9NQ94 factor (APOBEC1- stimulating protein) 31 FLAEHPNVTL Probable DNA dC->dU- Q96AK3 editing enzyme APOBEC- 3D (EC 3.5.4.-) 32 NLVQDSLDL Apolipoprotein-L4 pre- Q9BPW4 cursor (Apolipoprotein L-IV) 33 ISENEKLQK Apoptosis stimulating Q96KQ4 of p53 protein 1 34 VLAARNPAKV Nucleoporin 188 kDa Q5SRE5 (arachin) 35 RYFDGNLEKL Protein ariadne-1 homo- Q9Y4X5 log (ARI-1) (Ubiquitin- conjugating enzyme E2- binding protein 1) 36 TLADVLYHV Set1/Ash2 histone Q9UBL3 methyltransferase com- plex subunit ASH2 (ASH2-like protein) 37 LPSPKPMKMKN ATP synthase F0 subunit Q85KZ3 8 Splice isoform 2 of Q9H7F0 38 ISSMLVLFF ATPase_family_homo- Q9H7F0 log_up-regulated_in_ senescence_cells_ Probable phospholipid- transporting 39 SPDEGALVRA ATPase 1A (EC 3.6.3.1) Q9Y2Q0 (Chromaffin granule ATPase II) 40 ILLITLIPY ATP-binding cassette Q8WWZ4 A10 41 NLEQQETEP ATP-binding cassette Q9BZC7 sub-family A member 2 (ATP-binding cassette transporter 2) (ATP- binding cassette 2) 42 RKVLYVMEL Autoantigen RCD8 Q6P2E9 43 EAIPARKLK xonemal dynein heavy Q96JB1 chain 8 44 SLRLENITV Butyrophilin-like pro- Q6UX41 tein 8 precursor 45 SYVLKKAQV Ubiquitin carboxyl- Q9Y2K6 terminal hydrolase 20 (EC 3.1.2.15) 46 KLIHPKLEY Bardet-Biedl syndrome 7 Q8IWZ6 protein (BBS2-like protein 1) 47 EFDQLDQEN Large proline-rich pro- P48634 tein BAT2 (HLA-B-assoc- iated transcript 2) 48 TVLLRLGDEL Bcl-2 related ovarian killer 49 LFEILIEQI Lipopolysaccharide- P50851 responsive and beige- like anchor protein (CDC4-like protein) 50 KLELDETGQE Splice isoform 3 of P35612-3 P35612 51 LAIGAFTLLL UDP-GlcNAc: betaGal Q9Y2A9 beta-1,3-N-acetylgluco- saminyltransferase 3 (EC 2.4.1.-) 52 QILLDETLK Cell growth inhibiting Q2TTR2 protein 39 53 DECITNLLV BH3-interacting domain P55957 death agonist (BID) 54 TVVSGSNVILN CD48 antigen precursor P09326 (B-lymphocyte activa- tion marker BLAST-1) 55 SLDERPVAV Bone morphogenetic pro- Q13873 tein receptor type-2 precursor (EC 2.7.11.30) 56 MVDSQQKSP Bullous pemphigoid an- Q8WXK8 tigen 1, isoform 7 57 SLLLLPEKN BRCA1 associated RING Q53F80 domain 1 variant 58 VLCVSDIISL Breast cancer type 2 P51587 susceptibility protein (Fanconi anemia group D1 protein) 59 FLPDPSALQNL Protein BRE (Brain and Q9NXR7 reproductive organ- expressed protein) (BRCA1/BRCA2-containing complex subunit 45) 60 MLNEHDFEV Breast cancer 1 early Q3LRJ0 onset 61 VNTDFSPYL Breast cancer 1 early Q3LRJ0 onset 62 EFMLVYKFAR Breast and ovarian Q7KYU6 cancer susceptibility protein 63 TLWVDPYEV BTG2 protein (NGF- P78543 inducible anti-proli- ferative protein PC3) 64 FLDHIIASV Nuclear protein 5qNCA Q7LBC6 65 TLNDREYQL CAD protein [Includes: P27708 Glutamine-dependent carbamoyl-phosphate synthase (EC 6.3.5.5); Aspartate carbamoyl- transferase (EC 2.1.3.2); Dihydrooro- tase (EC 3.5.2.3)] 66 VEVMVNDVN Cadherin EGF LAG seven- Q9NYQ7 pass G-type receptor 3 precursor (Flamingo homolog 1) (hFmi 1) (Multiple epidermal growth factor-like do- mains 2) (Epidermal growth factor-like 1) 67 LSIYLSIYL Cadherin FIB3 Q6UW70 68 SLSMVNHRL Integrin alpha-3 pre- P26006 cursor (Galactoprotein B3) 69 RVDFPGFVR Calcineurin B homolo- O43745 gous protein 2 (Hepato- cellular carcinoma-as- sociated antigen 520) 70 MTDKAPPGV Calcium/calmodulin- Q7Z7J9 dependent protein ki- nase II inhibitor alpha (CaMKIINalpha) 71 WTNPQFKI Calpain-11 (EC Q9UMQ6 3.4.22.-) 72 IMAQLPQEQKA Alpha-1 catenin (Cad- P35221 herin-associated pro- tein) (Alpha E-catenin) 73 KIDPLEVEE Neural cell adhesion Q59FY0 molecule variant 74 KLPEKWESV Ribosomal L1 domain- O76021 containing protein 1 (Cellular senescence- inhibited gene protein) 75 LIEKEKVLN CENP-F kinetochore pro- P49454 tein (Centromere pro- tein F) (Mitosin) 76 FEVKEDQVK Centaurin-delta 1 (Cnt- Q8WZ64 d1) (Arf-GAP, Rho-GAP, ankyrin repeat and pleckstrin homology do- main-containing protein 2) 77 DTEAEKSQV Centrosomal protein 2 Q9BV73 (Centrosomal Nek2-as- sociated protein 1) (C- NAP1) 78 FLKEHMDEV Pericentriol material 1 Q15154 79 KLLGELHTL Pericentriol material 1 Q15154 80 TLVEAFPTL Cervical cancer sup- Q8NFX8 pressor gene 5 81 QSNKGFVVIN T-complex protein 1 Q92526 subunit zeta-2 82 LADGALIYR Chemokine-like factor Q9UBR5 (C32) 83 GLGAEIEIR Vacuolar protein Q96RL7 sorting 13A 84 GKLILLDKL Chromodomain-helicase- O14647 DNA-binding protein 2 (EC 3.6.1.-) 85 PQTICRKP FERM domain-containing Q96NE9 protein 6 86 RSYYLNEI Putative protein Q9H0A9 C21orf56 87 TTITVSPFY Adiponutrin (iPLA2- Q9NST1 epsilon) 88 RLPDDDPTAV Coatomer subunit gamma- Q9UBF2 2 89 LVAISTVSFSI Sodium/potassium/ Q9UI40 calcium exchanger 2 precursor 90 VLIDYQRNV Exportin-1 (Chromosome O14980 region maintenance 1 protein homolog) 91 SILNEGGIK CUB and sushi domain- Q7Z407 containing protein 3 precursor 92 YMADRLLGV Cullin-7 (CUL-7) Q14999 93 YLKDLIEEV Cyclic AMP-dependent P18848 transcription factor ATF-4 94 YLDIKGLLD S-phase kinase-associ- P63208 ated protein 1A (Cyclin A/CDK2-associated protein p19) 95 PCLSELHKA Cyclin-A1 P78396 96 TVLDFGVLASI Cyclin M3, isoform 1 Q8NE01 97 MPSETPQAE Cystathionine beta- Q58H57 synthase human homolog of Cynomolgus monkey gene product 98 FLLEALRKT Cytochrome P450 2E1 (EC P05181 1.14.14.1) 99 KMLETKWSL Keratin, type II cyto- P05787 skeletal 8 100 QPLLKQSPW CPEB2 protein Q3B8N6 101 YLLPAIVHI Probable ATP-dependent P17844 RNA helicase DDX5 (EC 3.6.1.-) 102 KLLPGDIHQI Dedicator of cytokine- Q14185 sis protein 1 103 SLLKGDLKGV Development and differ- O43150 entiation-enhancing factor 2 104 NAEVLLVSEI Probable ubiquitin O00507 carboxyl-terminal hy- drolase FAF-Y (EC 3.1.2.15) 105 RLWGEPVNL Probable ubiquitin car- O00507 boxyl-terminal hy- drolase FAF-Y (EC 3.1.2.15) 106 QLIDLSSPLI G2 and S phase ex- Q9NYZ3 pressed protein 1 107 YIDYTGAAYA HUMAN CDNA FLJ30829 Q96NI3 fis, clone FEBRA2001790, highly similar to Xenopus laevis RRM-containing protein SEB-4 mRNA 108 VIENKSDEKVI KIAA1799 protein Q96B95 109 PSPQLWTV Peroxisomal prolifera- Q9BYK8 tor-activated receptor A-interacting complex 285 kDa protein (EC 3.6.1.-) (ATP-dependent helicase PRIC285) 110 EGRGGLPAGLPV HUMAN KIAA1922 Q96PW6 111 NMYGKVVTV Transcription elonga- O00267 tion factor SPT5 (DLC- 1)(deleted in liver cancer-1) 112 RLYDGLFKV DNA damage-binding pro- Q16531 tein 1 (Damage-specific DNA-binding protein 1) 113 QNFVDSKEV DNA excision repair Q03468 protein ERCC-6 114 ALIEKLVEL DNA polymerase alpha Q14181 subunit B (DNA poly- merase alpha 70 kDa subunit) 115 VIEDDVNMAIR DNA replication licens- P49736 ing factor MCM2 (Mini- chromosome maintenance protein 2 homolog) 116 SQDEIKQEV DNA2-like homolog (EC P51530 3.6.1.-) (DNA replica- tion ATP-dependent hel- icase-like homolog) 117 HLNGSCHLLI Estrogen response ele- Q77798 ment binding protein (cotton-top Tarmarin), DNA2-like homolog (human) 118 ALIDRMVNL DNA damage-inducible P35638 transcript 3 (DDIT-3) (Growth arrest and DNA- damage-inducible pro- tein GADD153) 119 SQKIQEAVKA DNA-directed RNA poly- O95602 merase I largest sub- unit (EC 2.7.7.6) 120 LFDLVEEVQ DnaJ homolog subfamily Q96KC8 C member 1 121 LLAALLLDP Splice isoform 2 of P35462-2 P35462 122 FLDESRSTQYM RuvB-like 2 (EC Q9Y230 3.6.1.-) (48-kDa TATA box-binding protein- interacting protein) 123 VLLGKVYVV DRE1_protein Q9NXT9 124 TIDELKEQV Dynactin-1 (150 kDa Q14203 dynein-associated polypeptide) 125 NLAYENVKE Dynein heavy chain, Q14204 cytosolic (DYHC) 126 SEVEQYVKY Dynein heavy chain, Q14204 cytosolic (DYHC) 127 ETQLTYRR Echinoderm microtubule Q6UYC9 associated protein-like 5 128 IKDDLEDLI ECT2 protein (Epithel- Q9H8V3 ial cell-transforming sequence 2 oncogene) 129 QVLGKIERA Endothelial differenti- O60869 ation-related factor 1 (EDF-1) 130 IQINLQRKM Developmentally-regu- O43854 lated endothelial cell locus 1 protein) 131 KLIEKLDIKL Elongation factor 2 P13639 (EF-2) 132 YLNEIKDSV Elongation factor 2 P13639 (EF-2) 133 YLAEKYEWDV Elongation factor 2 P13639 (EF-2) 134 VFEESQVAGT Elongation factor 2 P13639 (EF-2) 135 DAQKEIVRAQK J domain protein Q9NX36 C21orf55 136 DLEETVFTAS J domain protein Q9NX36 C21orf55 137 AMLEGGVDGLL EMILIN-3 precursor Q9NT22 (EMILIN-5) (Elastin mi- crofibril interface- located protein 5) 138 RKADEKRIR Synaptotagmin-like pro- Q96C24 tein 4 (Exophilin-2) 139 ALQEMVHQV Enhancer of filamenta- Q14511 tion 1 (HEF1) 140 ILAINKPQNK Enhancer of filamenta- Q14511 tion 1 (HEF1) 141 SMYGVDLHHA Band 4.1-like protein 3 Q9Y2J2 (4.1B) (Differentially expressed in adenocar- cinoma of the lung pro- tein 1) (DAL-1) 142 SEDITRYYL Band 4.1-like protein 3 Q9Y2J2 (4.1B) (Differentially expressed in adenocar- cinoma of the lung pro- tein 1) (DAL-1) 143 NQQEQEDLE Epidermal growth factor P42566 receptor substrate 15 144 SKEEDPENV Epidermal growth factor P42566 receptor substrate 15 145 FLDKQGFYV Epidermal growth factor P42566 receptor substrate 15 (Protein Eps15) (AF-1p protein) 146 TGALIYAIHA Epithelial membrane P54852 protein 3 (EMP-3) (YMP protein) 147 AVQVLMVLSL Epithelial membrane P54852 protein 3 (EMP-3) (YMP protein) 148 TLKEVEELEQL Zyxin (Zyxin-2) Q15942 149 VLMTEDIKL Eukaryotic translation Q04637 initiation factor 4 gamma 1 150 EEKKQKEMD Eukaryotic translation Q04637 initiation factor 4 gamma 1 151 ELQALYALQAL Eukaryotic translation Q04637 initiation factor 4 gamma 1 152 WSNKYDPPL F-actin capping protein P47756 beta subunit 153 NLSDLIDLV F-actin capping protein P47756 beta subunit 154 FLSHKLDIK Protocadherin Fat 2 Q9NYQ8 precursor (hFat2) (Mul- tiple epidermal growth factor-like domains 1) 155 VEPALRKPP Protocadherin Fat 2 Q9NYQ8 precursor (hFat2) (Mul- tiple epidermal growth factor-like domains 1) 156 QVVYSLPDSA Protocadherin Fat 2 Q9NYQ8 precursor (hFat2) (Mul- tiple epidermal growth factor-like domains 1) 157 EKISSYQLK Protocadherin Fat 2 precursor (hFat2) (Mul- Q9NYQ8 tiple epidermal growth factor-like domains 1) 158 EMDPQKMPYL KIAA1752 protein Q9C0B1 159 VTNRARASKD Fc alpha/mu receptor Q8WWV6 160 SMNLTISAGP Fc alpha/mu receptor Q8WWV6 161 VTYLQNGKGR Low affinity immuno- P08637 globulin gamma Fc re- gion receptor III-A precursor (IgG Fc re- ceptor III-2) 162 ELLKTARSSK FYVE, RhoGEF and PH do- Q7Z6J4 main-containing protein 2 (Zinc finger FYVE do- main-containing protein 4) 163 LKEYIQKLP FYVE, RhoGEF and PH do- Q7Z6J4 main-containing protein 2 (Zinc finger FYVE do- main-containing protein 4) 164 YLNKLLITR Fibroblast growth fac- Q8N441 tor receptor-like 1 precursor (FGF recep- tor-like protein 1) 165 IARPVGSSVR Fibroblast growth fac- Q8N441 tor receptor-like 1 precursor (FGF recep- tor-like protein 1) 166 QCPVEGDPPPL Fibroblast growth fac- Q8N441 tor receptor-like 1 precursor (FGF recep- tor-like protein 1) 167 TEDNVMKIA Fibroblast growth fac- P22455 tor receptor 4 precur- sor (EC 2.7.10.1) 168 YLLDVLERS Fibroblast growth fac- P22455 tor receptor 4 precur- sor (EC 2.7.10.1) 169 TASPDYLEI Fibroblast growth fac- P21802 tor receptor 2 precur- sor (EC 2.7.10.1) (FGFR-2) 170 TENNVMKIA Fibroblast growth fac- P21802 tor receptor 2 precur- sor (EC 2.7.10.1) (FGFR-2) 171 ETFKQIDMDND FK506-binding protein 7 Q9Y680 precursor (EC 5.2.1.8) 172 GLLELIEEP Glomulin (FKBP-associa- Q92990 ted protein) (FK506- binding protein-assoc- iated protein) 173 FVEEVIDNK Glomulin (FKBP-associa- Q92990 ted protein) (FK506- binding protein-assoc- iated protein) 174 LQLYINKLD Glomulin (FKBP-associa- Q92990 ted protein) (FK506- binding protein-assoc- iated protein) 175 EQSLETTKV FKSG73 Q9BWW1 176 VFNDELPASI Flavin containing mono- Q53FW5 oxygenase 3 isoform 2 variant 177 SLFPGKLEV Protein flightless-1 Q13045 homolog 178 QKKLVDTIE Guanylate-binding pro- Q96PP9 tein 4 179 DVGKDQEFTV Filamin-A (Alpha- P21333 filamin) (Filamin-1) (Endothelial actin- binding protein) 180 YLLKDKGEYTL Filamin-A (Alpha- P21333 filamin) (Filamin-1) (Endothelial actin- binding protein) 181 KTTDDIVKV FLJ10101 protein Q8WU94 182 IEQERLER CDNA FLJ14503 fis, Q96T17 clone NT2RM1000252, weakly similar to H. sapiens E- MAP-115 mRNA 183 KINSAPSSPIK E2F8 protein Q5BKY4 184 NNDICLDEV Human Hypothetical Q2VPJ3 protein 185 VFAEVGCSPC HUMAN CDNA FLJ34154 Q8NB70 fis, clone FCBBF3013058 186 NIVETVLDL Hypothetical protein Q6ZUJ4 FLJ43654 (Hypothetical protein C3orf62) 187 IYIDGVQEVF HUMAN CDNA FLJ46180 Q6ZRQ5 fis, clone TESTI4004031 188 KIMTEKELLAV Flotillin-2 (Epidermal Q14254 surface antigen) (ESA) 189 VEAQEILR Flotillin-2 (Epidermal Q14254 surface antigen) (ESA) 190 MLLDFIQHI Serine/threonine-pro- Q13535 tein kinase ATR (EC 2.7.11.1) (Ataxia tel- angiectasia and Rad3- related protein) (FRAP- related protein 1) 191 SLLESVQKL Serine/threonine-pro- Q13535 tein kinase ATR (EC 2.7.11.1) (Ataxia tel- angiectasia and Rad3- related protein) (FRAP- related protein 1) 192 YLQPKLLGI Serine/threonine-pro- Q13535 tein kinase ATR (EC 2.7.11.1) (Ataxia tel- angiectasia and Rad3- related protein) (FRAP- related protein 1) 193 YLLVGTLFLL Frizzled 5 precursor Q13467 (Frizzled-5) 194 MAAGDYPEA Frizzled 5 precursor Q13467 (Frizzled-5) 195 LYLLVGTLFL Frizzled 5 precursor Q13467 (Frizzled-5) 196 ALSDHHVYL Fructose-bisphosphate P09972 aldolase C (EC 4.1.2.13) 197 YLAPHVRTL G protein pathway sup- Q53HS2 pressor 1 isoform 1 variant 198 YLQNWSHVL G protein pathway sup- Q53HS2 pressor 1 isoform 1 variant 199 FAALMLLGLV KiSS-1 receptor (KiSS- Q969F8 1R) (Kisspeptins recep- tor) (Metastin recep- tor) (G-protein coupled receptor 54) 200 MINLAVFDL Probable G-protein Q9Y2T6 coupled receptor 55 201 EASALAVAPSAK Probable G-protein Q9HC97 coupled receptor 35 202 TFVLTIILV G-protein coupled re- Q9NQ84 ceptor family C group 5 member C precursor (Retinoic acid-induced gene 3 protein) 203 FLLDFEEDL Leucine-rich repeat- O75473 containing G-protein coupled receptor 5 pre- cursor (Orphan G-pro- tein coupled receptor HG38) (G-protein coupled receptor 49) (G-protein coupled re- ceptor 67) 204 FAMDSYGTSN Probable G-protein Q6QNK2 coupled receptor 133 precursor (G-protein coupled receptor PGR25) 205 MELSEPIVEN G1 to S phase transi- P15170 tion protein 1 homolog (GTP-binding protein GST1- HS) 206 WLENALGKL Gamma-aminobutyric-acid Q16445 receptor alpha-6 sub- unit precursor (GABA(A) receptor) 207 KILEHDDVSYL Ganglioside-induced Q96MZ0 differentiation-assoc- iated protein 1-like 1 (GDAP1-L1) 208 SQQNTDNLV Gap junction alpha-5 P36382 protein (Connexin-40) (Cx40) 209 SKLCEETPI GEM-interacting protein Q9P107 (GMIP) 210 QLVVELKDI Golgin subfamily B Q14789 member 1 (Giantin) 211 VFDIFQFAK UDP-N-acetylhexosamine Q16222 pyrophosphorylase (Antigen X) 212 NIANHFFTV UDP-N-acetylhexosamine Q16222 pyrophosphorylase (Antigen X) 213 HLIHEVTKV Neutral alpha-glucosi- Q14697 dase AB precursor (EC 3.2.1.84) 214 FLDPNNIPKA Probable dolichyl pyro- Q9BVK2 phosphate Glc1Man9GlcNAc2 alpha- 1,3-glucosyltransferase (EC 2.4.1.-) 215 KINEAVECLLSL Bifunctional aminoacyl- P07814 tRNA synthetase [In- cludes: Glutamyl-tRNA synthetase (EC 6.1.1.17) (Glutamate-- tRNA ligase); Prolyl- tRNA synthetase (EC 6.1.1.15) (Proline-- tRNA ligase)] 216 LLQTPKLLL Glycoprotein nmb-like Q8IXJ5 protein 217 VLLYSVVVV Prolactin-releasing P49683 peptide receptor (PrRP receptor) (PrRPR) (G- protein coupled recep- tor 10) 218 KFKQCKLLQ G protein-coupled re- Q5EGP2 ceptor 112 219 DVLSTSSAISL G protein-coupled re- Q5EGP2 ceptor 112 220 YIDDHSWTL Growth factor receptor- Q14449 bound protein 14 (GRB14 adapter protein) 221 SLYEENNKL GRIP and coiled-coil Q8IWJ2 domain-containing pro- tein 2 (Golgi coiled coil protein GCC185) (CTCL tumor antigen se1-1) 222 KLLEVQILE GRIP and coiled-coil Q8IWJ2 domain-containing pro- tein 2 (Golgi coiled coil protein GCC185) (CTCL tumor antigen se1-1) 223 KPLLEQKEL GRIP and coiled-coil Q8IWJ2 domain-containing pro- tein 2 (Golgi coiled coil protein GCC185) (CTCL tumor antigen se1-1) 224 FPWELDPDWS GROS1-L protein Q9HC86 225 YLSAAINPIL Growth hormone secreta- Q92847 gogue receptor type 1 (GHS-R) 226 QLSLADVILL Glutathione S-transfer- O15217 ase A4-4 (EC 2.5.1.18) 227 QSFLVGNQL Glutathione S-transfer- O15217 ase A4-4 (EC 2.5.1.18) 228 LKNKTKEAAE GTP-binding protein Q96D21 Rhes (Ras homolog en- riched in striatum) (Tumor endothelial marker 2) 229 EDFHRKVYNI GTP-binding protein Q96D21 Rhes (Ras homolog en- riched in striatum) (Tumor endothelial marker 2) 230 YIDDVFHAL GTP-binding protein Q92963 Rit1 (Ras-like protein expressed in many tissues) 231 EQLAELRQEF VGFG2573 Q6UY45 232 GLLERVKEL Hypothetical protein Q53QU2 HDLBP 233 DAILRIVGE Hypothetical protein Q53QU2 HDLBP 234 RHKLVSDGQ Heat shock protein 75 Q12931 kDa, mitochondrial pre- cursor (HSP 75) (Tumor necrosis factor type 1 receptor-associated protein) 235 IQLVMKVIE Heat shock protein Q53ZP9 apg-1 236 MTREELVKN Tumor rejection antigen Q5CAQ5 (Gp96) 1 237 ALKDKIEKA Tumor rejection antigen Q5CAQ5 (Gp96) 1 238 KIILRHLIE Heat-shock protein Q12988 beta-3 (HspB3) (Heat shock 17 kDa protein) 239 TLGKLFWV Low-density lipoprotein O75197 receptor-related pro- tein S precursor 240 KGQGGAGGQFL Regulator of telomere Q9NZ71 elongation helicase 1 (EC 3.6.1.-) (Helicase- like protein NHL) 241 KEFLVVASV Hematopoietic protein 1 Q52LW0 242 KIAQKALDL Heme oxygenase 1 (EC P09601 1.14.99.3) (HO-1) 243 ITEPLPELQL Heparan sulfate gluco- Q8IZT8 samine 3-O-sulfotrans- ferase 5 (EC 2.8.2.23) 244 KLRKEKEEF Hepatocellular carcin- Q9NYH9 oma-associated antigen 66 245 EDVFPNILN Melanoma-associated an- Q8TD90 tigen E2 (MAGE-E2 an- tigen) (Hepatocellular carcinoma-associated protein 3) 246 IAVMLLEGGAN 26S proteasome non- O75832 ATPase regulatory sub- unit 10 (26S proteasome regulatory subunit p28) 247 VDLFPGTFEV Hepatocellular carcin- Q5JUU1 oma-associated protein p28-II Hephaestin 248 MVCGSPDIPL HECT domain and RCC1- O95714 like domain-containing protein 2 (HERC2) 249 DAPHSEGDMHLL HECT domain and RCC1- O95714 like domain-containing protein 2 (HERC2) 250 DTIEIITDR Heterogeneous nuclear P22626 ribonucleoproteins A2/ B1 (hnRNP A2/hnRNP B1) 251 RLFVGSIPK Heterogeneous nuclear O43390 ribonucleoprotein R (hnRNP R) 252 FLSEYQHQP HEXIM1 protein (HMBA- O94992 inducible) 253 LALMISMISAD Histatin-1 precursor His- (Histidine-rich protein tatin-1 1) precur- sor (Histi- dine- rich protein 1) 254 RMLPHAPGV Histone deacetylase 1 Q13547 (HD1) 255 THNLLLNYGL Histone deacetylase 1 Q13547 (HD1) 256 SPNMNAVISL Histone deacetylase 9 Q9UKV0 (HD9) (HD7B) (HD7) 257 EFIDLLKKM Homeodomain-interacting Q9H2X6 protein kinase 2 (EC 2.7.11.1) 258 KMINHDSEKED Cullin-2 (CUL-2) Q13617 259 AVDEDRKMYL Cullin-2 (CUL-2) Q13617 260 LFELLEKEI SWI/SNF-related matrix- O60264 associated actin-de- pendent regulator of chromatin subfamily A member 5 (EC 3.6.1.-) 261 FISEFEHRV HUMAN HSPC027 26S pro- Q9Y6E3 teasome non-ATPase regulatory subunit 13 Synonyms 26S proteasome regulatory subunit S11 26S proteasome regula- tory subunit p40.5 262 AMFDHIPVGV Hypothetical protein Q9Y310 (Novel protein HSPC117) (DJ149A16.6 protein) (Hypothetical protein HSPC117) 263 WSFCLACV Claudin domain-contain- Q9NY35 ing protein 1 (Membrane protein GENX-3745) Q9NY35 264 NLLFPIIYL Large neutral amino Q9UHI5 acids transporter small subunit 2 (L-type amino acid transporter 2) (hLAT2) 265 SLLENLEKI Heterogeneous nuclear O60812 ribonucleoprotein C- like 1 (hnRNP core protein C-like 1) 266 ILDQKINEV Ornithine decarboxylase P11926 (EC 4.1.1.17) (ODC) 267 DQINIETKN Regulator of nonsense Q9HAU5 transcripts 2 (Nonsense mRNA reducing factor 2) (Up-frameshift suppres- sor 2 homolog) (hUpf2) 268 PFQNLLKEY Regulator of nonsense Q9HAU5 transcripts 2 (Nonsense mRNA reducing factor 2) (Up-frameshift suppres- sor 2 homolog) (hUpf2) 269 LELELENLEI Regulator of nonsense Q9HAU5 transcripts 2 (Nonsense mRNA reducing factor 2) (Up-frameshift suppres- sor 2 homolog) (hUpf2) 270 GLADASLLKKV ATX10_HUMAN Ataxin-10 Q9UBB4 271 GQILEAAVSV KIAA1833 protein Q569G6 272 RVVSVSFRV HUMAN UDP-GalNAc: Q8NCR0 betaGlcNAc beta 1,3- galactosaminyltransfer- ase, polypeptide 2 (Beta 1,3-N-acetylgal- actosaminyltransferase- II) (MGC39558) 273 TQKRLDVYL Hypothetical protein Q2M389 KIAA1033 274 AMLTVLHEI Activating signal coin- Q8N3C0 tegrator 1 complex sub- unit 3 (EC 3.6.1.-) 275 ARLAALVQR Delta-interacting pro- Q15834 tein A (Hepatitis delta antigen-interacting protein A) (Coiled-coil domain-containing pro- tein 85B) 276 FAVHFYRS Hypothetical protein Q96BP7 FLJ14466 277 FNITYLDID Interferon-inducible O75569 double stranded RNA- dependent protein kinase activator A 278 GLAKRVWSL Hypothetical protein Q9BUH6 C9orf142 279 HLDATKLLL Tetratricopeptide re- Q96AE7 peat protein 17 280 IGSFHGVLSL CDNA FLJ14058 fis, Q9H7Z0 clone HEMBB1000554 281 ILDLIDDAW Anaphase promoting com- Q9BS18 plex subunit 13 282 KLLEMVRED Hypothetical protein Q8IWA6 CCDC60 283 LSYLPATVEP Sphingosine kinase 2 Q9NRA0 (EC 2.7.1.-) 284 QLAQFVHEV Probable ATP-dependent Q96FC9 RNA helicase DDX11 (EC 3.6.1.-) (DEAD/H box protein 11) (CHL1 homo- log) (Keratinocyte growth factor-regulated gene 2 protein) (KRG-2) 285 SYDESDEEE Protein KIAA0182 Q14687 286 SYSDEFGPS Ras GTPase-activating Q96PV0 protein SynGAP (Synap- tic Ras-GTPase-activat- ing protein 1) (Synap- tic Ras-GAP 1) (Neuro- nal RasGAP) 287 TVERADSSHLSI Fibrinogen C domain Q8N539 containing 1 288 VTENELAVIT MGC39581 protein Q86XM0 289 VTYLEDYSA Bcl-2-like 13 protein Q9BXK5 (Mill protein) (Bcl-rambo) 290 YLLEKTRVA Myosin head domain con- Q96H55 taining 1 291 TLKILDLME WD-repeat protein 51A Q8NBT0 292 EDLIKELIK KIF27A Q86VH2 (OTTHUMP00000021559) 293 LSLENLEKI Inositol polyphosphate- Q2T9J4 5-phosphatase F, isoform 1 294 FLNKAADFIE Myopalladin Q96KF5 295 GLDIDGIYRV Rho GTPase activating Q5T2Y2 protein 12 296 QNNNLQTQI Hypothetical protein Q7Z3C5 DKFZp686D0630 297 FLDDVVHSL Jumonji domain-contain- Q15652 ing protein 1C (Thyroid receptor-interacting protein 8) (TRIP-8) 298 NMVDLNDY Coatomer subunit beta P53618 (Beta-coat protein) (Beta-COP) 299 YLLKEDMAGI FLJ10462 fis, clone Q9NVW8 NT2RP1001494, weakly similar to MALE STERILITY PROTEIN 2 300 KLFEKVKEV FLJ10462 fis, clone Q9NVW8 NT2RP1001494, weakly similar to MALE STERILITY PROTEIN 2 301 TVMDEIHTV Cell-cycle and apopto- Q6X935 sis regulatory protein 1 302 KLISELQKL Telomere-associated Q5UIP0 protein RIF1 (Rap1-in- teracting factor 1 hom- olog) 303 KVIDEIYRV F-box only protein 28 Q9NVF7 304 SSLSDGLLLE CDNA FLJ10901 fis, Q9NV65 clone NT2RP5003524 305 EEIVKVTFE Acetoacetyl-CoA synthe- Q86V21 tase (EC 6.2.1.16) 306 ELLENIIKN Putative cell cycle Q9NXZ0 control protein (DEP domain containing 1) 307 ELLSLVQNL Synaptopodin 2-like Q68A20 308 PQQERDFY CDNA FLJ36560 fis, Q8N9T8 clone TRACH2009340 309 GRGGKDPPLEP CDNA FLJ13330 fis, Q9H8Q0 clone OVARC1001802 310 LADISLHDPV ATP-dependent RNA heli- Q9H8H2 case DDX31 (EC 3.6.1.-) (DEAD box protein 31) (Helicain) 311 PSNMGIAIPL Protein C14orf161 Q9H7T0 312 FMMPQSLGV Cysteine protease ATG4B Q9Y4P1 (EC 3.4.22.-) (Auto- phagy-related protein 4 homolog B) 313 IMVATAVVAI CDNA FLJ14526 fis, Q96T08 clone NT2RM1001139 314 MTKRYEALE Hypothetical protein Q9BR77 CCDC77 (CDNA FLJ14732 fis, clone NT2RP3001969, weakly similar to TRICHOHYALIN) 315 SLDAKEIYL CDNA FLJ14790 fis, Q96K38 clone NT2RP4000973, weakly similar to PROBABLE PROTEIN DI- SULFIDE ISOMERASE P5 (EC 5.3.4.1) 316 QLLDIKTRL Keratin 24 Q2M215 317 FLTDYLNDL BCoR protein (BCL-6 Q6W2J9 corepressor) 318 ANQGGFENGE Hypothetical protein Q61Q21 FLJ20582 319 ILGLLLLHLE Hypothetical protein Q9BT04 FLJ22688 320 VYQKEGVLAS Hypothetical protein Q9H5W3 FLJ22944 321 YLNDFTHEI Zinc finger protein, Q8TBE5 subfamily 1 A, 5- 322 SPPLQGEIS Leucine-rich repeats Q8IW35 and IQ motif containing 2 323 LFFEPVTTP Hypothetical protein Q8TEA0 FLJ23749 http:// www.e xpasy. org/spr 324 WISVPVVT Hypothetical protein ot/user FLJ25336 man.ht ml-AC_(—) lineQ96L P1 325 NMEIMPEGSL Hypothetical protein Q8N7G6 FLJ25660 326 QDQLSALQL CDNA FLJ30058 fis, Q96NU6 clone ADRGL2000074, weakly similar to RHO-GIPASE- ACTIVATING PROTEIN 6 327 MEADPDLSR CDNA FLJ30106 fis, Q96A82 clone BNGH41000190, weakly similar to Rattus norvegicus schlafen-4 (SLFN- 4) mRNA. 328 LYLPATTPY Whirlin Q9P202 329 SEIEKNKKV CDNA FLJ31846 fis, Q96MV0 clone NT2RP7000425, weakly similar to MYOSIN HEAVY CHAIN, NONMUSCLE TYPE B 330 SLVQIVTTL FLJ32833 fis, clone Q96M43 TESTI2003228 331 KILDIRKNV Guanine nucleotide- P38405 binding protein G(olf), alpha subunit (Adenylate cyclase- stimulating G alpha protein, olfactory type) 332 QSLELLLLPV CDNA FLJ33811 fis, Q8N279 clone CTONG2002095 333 ALLNNIIEI Transmembrane protein Q9BYT9 16C 334 FNQSSSLIIH Zinc finger protein 31 P17040 (Zinc finger protein KOX29) (Zinc finger and SCAN domain-containing protein 20) (Zinc finger protein 360) 335 LSLSALPVSY Transmembrane 6 Q9BZW4 superfamily member 2 336 YLDLTPNQE CDNA FLJ90251 fis, Q8NCH3 clone NT2RM4000115 337 YLFERIKEL CDNA FLJ90251 fis, Q8NCH3 clone NT2RM4000115 338 FILDVLLPEA CDNA FLJ90760 fis, Q8N2I4 clone THYRO1000061 339 EFIPEFEK Tubulin--tyrosine Q14166 ligase-like protein 12 340 DVFPATPGSQN KIAA0303 protein O15021 341 FIFDVHVHEV Plexin-B2 precursor O15031 (MM1) 342 ILEVTNNLE Zinc finger and BTB O15062 domain-containing protein 5 343 ILSKKDLPL Centrosome-associated Q8WY20 protein 350 344 HEPPKAVDK piccolo (Aczonin) Q9Y6V0 345 ILDDSHLLV KIAA0560 protein O60306 346 YLDNVVNKQ KIAA0676 protein Q96H49 347 KLLPYVGLLQ Human homolog of Mus Q810B7 SLIT and NTRK-like protein 5 precursor 348 QLKSLIQID Human homolog of Mus Q810B7 SLIT and NTRK-like protein 5 precursor 349 SLLNNPLSI Nischarin Q6PIB4 350 SSLSDALVLE FERM domain-containing Q9P2Q2 protein 4A 351 DELQQLFNL Leucine-rich repeats Q6UXK5 neuronal protein 1 pre- cursor (Neuronal leu- cine-rich repeat pro- tein 1) (NLRR-1) 352 QILSGRKPEL KIAA1512 protein Q9P216 353 KLVEVIEEV KIAA1598 protein Q9HCH4 354 QTLLKNPLY hosphatidylinositol-3 Q96QU2 phosphate 3-phosphatase adaptor subunit 355 SLLDDLHSA KIAA1730 protein Q9C0D3 356 HILDSSIYS KIAA1786 protein Q96JN9 357 QSSPPPPPPS Hypothetical protein Q96EK3 MGC20470 358 LMCYAIMVT OACT1 protein Q86XC2 359 FLSEEGGHVAV 6-phosphofructo-2-ki- Q16877 nase/fructose-2,6-bi- phosphatase 4 (6PF-2-K/ Fru-2,6-P2ASE testis- type isozyme) 360 SPDQELVLL IkappaB kinase complex- O95163 associated protein (IKK complex-associated pro- tein) (p150) 361 FLLVVLLKL Immune receptor ex- Q7Z7I3 pressed on myeloid cells 2 362 QIIEANYHS High-affinity cAMP- O60658 specific and IBMX-in- sensitive 3,5-cyclic phosphodiesterase 8A (EC 3.1.4.17) 363 ILIDKSGKLEL Bone specific CMF608 Q6WRI0 364 TVMDSKIVQV Importin alpha-7 sub- O60684 unit (Karyopherin alpha-6) 365 VMDSKIVQV Importin alpha-7 sub- O60684 unit (Karyopherin alpha-6) 366 YQDPLDPTRSV InaD-like protein Q8NI35 (Inadl protein) (hINADL) (Pals1-assoc- iated tight junction protein) (Protein as- sociated to tight junctions) 367 HEFLTPRL InaD-like protein Q8NI35 (Inadl protein) (hINADL) (Pals1-assoc- iated tight junction protein) (Protein as- sociated to tight junctions) 368 GLFPWTPKL InaD-like protein Q8NI35 (Inadl protein) (hINADL) (Pals1-assoc- iated tight junction protein) (Protein as- sociated to tight junctions) 369 CDVQRYNI Nitric oxide synthase, P35228 inducible (EC 1.14.13.39) 370 NMYGKVVTV Transcription elonga- O00267 tion factor SPT5 (hSPT5) 371 QNVQVNQKV Inositol-trisphosphate P27987 3-kinase B (EC 2.7.1.127) (Inositol 1,4,5-trisphosphate 3- kinase B) 372 SLINQMTQV Type I inositol-3,4- Q96PE3 bisphosphate 4-phospha- tase (EC 3.1.3.66) (Inositol polyphosphate 4-phosphatase type I) 373 NVTVAVPTV Insulin receptor beta Q9UCB7 subunit 374 LGLENLCHL Insulin-like growth Q8TAY0 factor binding protein, acid labile subunit 375 YYEKLHTYF Integrin beta-4 precur- P16144 sor (GP150) (CD104 antigen) 376 LLAALLLDP Splice isoform 2 of P35462-2 P35462 377 RRDFGFPQ Interferon alpha 2 Q16055 protein 378 SLLGFVYKL Interferon-induced pro- P09914 tein with tetratrico- peptide repeats 1 (IFIT-1)) (Interferon- induced 56 kDa protein) (IFI-56K) 379 LDRVFKNY Interleukin-20 precur- Q9NYY1 sor (IL-20) (Four alpha helix cytokine Zcyto10) 380 LMVDHVTEV Steroid receptor RNA Q9HD15 activator isoform 1 381 KMDQQEFSI Intersectin-2 (SH3 do- Q9NZM3 main-containing protein 1B) (SH3P18) (SH3P18- like WASP-associated protein) 382 SLLLLPEEL ITI-like protein (In- Q6UXX5 ter-alpha (Globulin) inhibitor H5-like) 383 SQQNTDNLV Gap junction alpha-5 P36382 protein (Connexin-40) 384 WLDETLAQV Kelch-like protein 8 Q9P2G9 385 VNLGGSKSISIS Keratin, type II cyto- P04264 skeletal 1 (Cytokera- tin-1) 386 ANYLDSMYI ADAM 9 precursor (EC Q13443 3.4.24.-) (A disinte- grin and metallopro- teinase domain 9) (Met- alloprotease/disinte- grin/cysteine-rich pro- tein 9) (Myeloma cell metalloproteinase) 387 HLWNSIHGL Next to BRCA1 gene 1 Q14596 protein (Neighbor of BRCA1 gene 1 protein) (Membrane component, chromosome 17, surface marker 2) (1A1-3B) 388 SLADLMPRV Hypothetical protein Q6MZZ8 DKFZp686K2075 389 IDLSASLVLN KIAA0100 protein Q14667 390 HLTYLNVYL Pre-mRNA-splicing fac- Q92620 tor ATP-dependent RNA helicase PRP16 (EC 3.6.1.-) (ATP-dependent RNA helicase DHX38) (DEAH box protein 38) 391 QLVACIESKL KIAA0251 protein Q8TBS5 392 EGKLVVQDIE HUMAN KIAA0342 protein O15050 393 QALEAGAVVLI KIAA0357 protein O15064 394 VLSCSQALKI Hypothetical protein Q6PGP7 KIAA0372 395 LSIEGEQEL KIAA0377 splice variant Q86TE7 2 396 EFQDLNQEV KIAA0386 protein Q9Y4F9 397 RTKLTDIQI HUMAN CTCL tumor anti- Q548S1 gen HD-CL-04 398 RECKYDLPP Importin-13 (Imp13) O94829 (Ran-binding protein 13) 399 QLTKIQTEL KIAA0769 protein O94868 400 LVNAAQSVFV Hypothetical protein Q61Q32 KIAA0863 401 VKAEDKARV Zinc finger protein Q96KM6 KIAA1196- 402 VLHDRIVSV CRSP complex subunit 3 Q9ULK4 (Cofactor required for Sp1 transcriptional activation subunit 3) (Transcriptional co- activator CRSP130) (Vitamin D3 receptor- interacting protein complex 403 RNSIATLQGGR 130 kDa component Q9P2J9 [Pyruvate dehydrogenase [lipoamide]]-phospha- tase 2, mitochondrial precursor (EC 3.1.3.43) 404 TVNILIVDQN Protocadherin-10 Q9P2E7 precursor 405 YLFDLPLKV Leucine-rich repeats Q5VUJ6 and calponin homology (CH) domain containing 2 406 NLAKDNEVL Ankyrin repeat domain Q5W0G2 18B 407 SGDKLKLDQT Kin17 protein (HsKin17 O60870 protein) (KIN, antigen- ic determinant of recA protein homolog) 408 KLTDYQVTL Kinesin-like protein Q9H1H9 KIF13A (Kinesin-like protein RBKIN) 409 KIQEILTQV Putative RNA binding O00425 protein KOC 410 YLDEQIKKV HUMAN Kinesin-like pro- Q9H1H9 tein KIF13A (Kinesin- like protein RBKIN) 411 SSIWEVDSLH HUMAN Kinesin-like pro- Q9H1H9 tein KIF13A (Kinesin- like protein RBKIN) 412 RLASYLDRV Keratin, type I cyto- P05783 skeletal 18 (Cytokeratin-18) 413 ALLNIKVKL Keratin, type I cyto- P05783 skeletal 18 (Cytokeratin-18) 414 FNIVKNKTE Kv3.2d voltage-gated Q86W09 potassium channel 415 KAITAPVSL Lethal(3)malignant Q9Y468 brain tumor-like pro- tein (L(3)mbt-like) (L(3)mbt protein homolog) 416 HEYLKAFKV Lactadherin precursor Q08431 (Milk fat globule-EGF factor 8) (MFG-E8) (HMFG) (Breast epithe- lial antigen BA46) (MFGM) 417 LKAFKVAYS Lactadherin precursor Q08431 (Milk fat globule-EGF factor 8) (MFG-E8) (HMFG) (Breast epithe- lial antigen BA46) (MFGM) 418 RLAVYIDRV Lamin-A/C (70 kDa P02545 lamin) 419 YLLGNSSPRT Lamin-A/C (70 kDa P02545 lamin) 420 EMKVSDLDR Laminin gamma-1 chain P11047 precursor (Laminin B2 chain) 421 VRLVDAGGVKL Low-density lipoprotein O75197 receptor-related pro- ein 5 precursor 422 KPETFEHLF Leptin receptor precur- P48357 sor (LEP-R) (OB receptor) 423 EITDDGNLK Leptin receptor precur- P48357 sor (LEP-R) (OB receptor) 424 ECHHRYAEL Leptin receptor precur- P48357 sor (LEP-R) (OB receptor) 425 PSTCPDGFKI Mitogen-activated pro- O43283 tein kinase kinase ki- nase 13 (EC 2.7.11.25) 426 RKGIIDVNL Leukemia virus receptor Q08357 2 427 LIQERDVKK Leukemia-associated Q8NFU7 protein with a CXXC domain 428 LTLEQVVAIE Leukemia-associated Q8NFU7 protein with a CXXC domain 429 RDTPHSDFRG RNA-binding protein 6 P78332 (RNA-binding motif pro- tein 6) (RNA-binding protein DEF-3) (Lung cancer antigen NY-LU- 12) 430 HRVLLHLF Lung cancer oncogene 5 Q7Z5Q7 431 LLFDRPMHV Heterogeneous nuclear P52272 ribonucleoprotein M (hnRNP M) 432 FLSELTQQL Macrophage migration P14174 inhibitory factor (MIF) (Phenylpyruvate tauto- merase) (EC 5.3.2.1) 433 SLLSHVEQL Mitotic spindle assem- Q9UI95 bly checkpoint protein MAD2B (MAD2-like 2) (hREV7) 434 KLILRLHKL Mitogen-activated pro- Q9Y6R4 tein kinase kinase ki- nase 4 (EC 2.7.11.25) (MAPK/ERK kinase kinase 4) 435 RLTHHPVYI Serine/threonine/tyro- Q9Y6J8 sine-interacting-like protein 1 (Dual-speci- ficity protein phospha- tase 24) (Map kinase phosphatase-like pro- tein MK-STYX) 436 QDNLEKLLQ Microtubule-associated Q6P0Q8 serine/threonine-pro- tein kinase 2 (EC 2.7.11.1) 437 MKRLLLLF Matrix metalloprotease Q9H306 MMP-27 438 DPQDILEVK MCM10 protein Q7L590 439 FLFGEVHKA MCM10 protein Q7L590 440 KVIVLVNKVLL Interferon-induced hel- Q9BYX4 icase C domain-contain- ing protein 1 (EC 3.6.1.-) (Melanoma dif- ferentiation-associated protein 5) 441 QILSLEEKI Melanoma ubiquitous Q2TAK8 mutated protein 442 MLKDIIKEY Melanoma antigen family Q5BJF3 D, 2 443 KTWGQYWQV Melanocyte protein Pmel P40967 17 precursor (Melano- cyte lineage-specific antigen GP100) 444 LLDGTATLRL Melanocyte protein Pmel P40967 17 precursor (Melano- cyte lineage-specific antigen GP100) 445 VLKEIVERV GPI-anchored protein Q14444 p137 (p137GPI) (Mem- brane component chromo- some 11 surface marker 1) Cytoplasmic activa- tion/proliferation- associated protein 1 446 SLLDEFYKL GPI-anchored protein Q14444 p137 (p137GPI) (Mem- brane component chromo- some 11 surface marker 1) Cytoplasmic activa- tion/proliferation- associated protein 1 447 TLNQNGYTLV Hepatocyte growth fac- P08581 tor receptor precursor (EC 2.7.10.1) (HGF re- ceptor) (Scatter factor receptor) (SF receptor) (HGF/SF receptor) (Met proto-oncogene tyrosine kinase) 448 QMPKMNFAN Mitogen-activated pro- Q16539 tein kinase 14 (EC 2.7.11.24) 449 KLADFGVSGE Mitogen-activated pro- Q12851 tein kinase kinase ki- nase kinase 2 (EC 2.7.11.1) (MAPK/ERK kinase kinase kinase 2) 450 SIKDYEQAN Mitotic kinesin-related Q96Q89 protein 451 EDLMEDEDL Mitotic kinesin-related Q96Q89 protein 452 VLISKELISL Sperm-associated anti- Q96R06 gen 5 (Astrin) (Mitotic spindle-associated pro- tein p126) 453 LIEKVQEAR Myeloid/lymphoid or Q9UMN6 mixed-lineage leukemia protein 4 (Trithorax homolog 2) 454 SRVRMKTPT Myeloid/lymphoid or Q9UMN6 mixed-lineage leukemia protein 4 (Trithorax homolog 2) 455 GLDDIKDLKV Putative helicase MOV- Q9HCE1 10 (EC 3.6.1.-) (Molo- ney leukemia virus 10 protein) 456 VLAETLTQV MOZ/CBP protein Q712H6 457 DTNADKQLS Calgranulin B (Migra- P06702 tion inhibitory factor- related protein 14) (MRP-14) (P14) 458 GRWVCKDLPCP MUC2_HUMAN Mucin-2 pre- Q02817 cursor (Intestinal mucin 2) 459 FGNMQKINQ MUC2_HUMAN Mucin-2 pre- Q02817 cursor (Intestinal mucin 2) 460 FPNWTLAQV Mucin-5B precursor Q9HC84 (Mucin 5 subtype B, tracheobronchial) 461 ATPSSTPETV Mucin-5B precursor Q9HC84 (Mucin 5 subtype B, tracheobronchial) 462 FVNDVNLEN Multiple PDZ domain O75970 protein (Multi PDZ do- main protein 1) (Multi- PDZ-domain protein 1) 463 SENKLILMK RUFY2 (Run and FYVE do- Q81W33 main-containing protein Rabip4 464 TFCVQPGEKV Multidrug resistance- Q8NHX7 associated protein 7 465 YLNDGLWHM Multiple copies in a Q9ULC4 T-cell malignancies (Malignant T cell am- plified sequence 1) (MCT1) 466 GTTLRNLEI DNA mismatch repair P20585 protein Msh3 467 SPPTLNGAPSP Protein CBFA2T2 (MTG8- O43439 like protein) (MTG8- related protein 1) (Myeloid translocation- related protein 1) 468 NEAAIKNVYL Myomesin-1 (190 kDa P52179 titin-associated pro- tein) (190 kDa connec- tin-associated protein 469 FIDFGMDLQ Myosin heavy chain, P12883 cardiac muscle beta isoform (MyHC-beta) 470 LLEAKVKEL Myosin-13 (Myosin heavy Q9UKX3 chain, skeletal muscle, extraocular) (MyHC-eo) 471 LLAEKVEQL Tumor suppressor candi- Q13454 date 3 (N33 protein) 472 LANARGLGLQ Nebulin-related anchor- Q8TCH0 ing protein 473 VNRIGQESLE Neural cell adhesion P13592 molecule 1, 1 474 YLEIQGITR Neurotrimin precursor Q9P121 475 EALENNKEL Ninein Q8N4C6 476 NSMVVERQQL Ninein Q8N4C6 477 HLLERVDQV Ninein Q8N4C6 478 PERTQLLYL Notch homolog 2 QSVTD0 479 NGGTCEDGIN Neurogenic locus notch P46531 homolog protein 1 pre- cursor (Notch 1) (hN1) (Translocation-associa- ted notch protein TAN- 1) [Contains: Notch 1 extracellular trunca- tion; Notch 1 intracel- lular domain] 480 QSAADYLGAL Neurogenic locus notch Q9UM47 homolog protein 3 pre- cursor (Notch 3) [Con- tains: Notch 3 extra- cellular truncation; Notch 3 intracellular domain] 481 ALLVVLSPPAL Neurogenic locus notch Q99466 homolog protein 4 pre- cursor (Notch 4) (hNotch4) [Contains: Notch 4 extracellular truncation; Notch 4 intracellular domain]- 482 LRLDXLFKL Plexin-A1 precursor Q9UIW2 (Semaphorin receptor NOV) 483 WLIEDGKVV HUMAN NPD011 Q9H2R7 484 SQPQEPENK Nuclear autoantigen Sp- P23497 100 (Speckled 100 kDa) (Nuclear dot-associated Sp100 protein) 485 LLREKVEFL Nuclear factor eryth- Q14494 roid 2-related factor 1 (NF-E2-related factor 1) (NFE2-related factor 1) (Nuclear factor, erythroid derived 2, like 1) (Transcription factor 11) (Transcrip- tion factor HBZ17) (Transcription factor LCR-F1) (Locus control region-factor 1) 486 YLDDVNEII Nuclear factor of acti- O95644 vated T-cells, cyto- plasmic 1 (NFAT trans- cription complex cyto- solic component) (NF- ATc1) 487 ALLDQLYLA Nuclear receptor co- Q15596 activator 2 (NCoA-2) (Transcriptional in- termediary factor 2) 488 TLFDYEVRL Ubiquitin-like PHD and Q96T88 RING finger domain-con- taining protein 1 (EC 6.3.2.-) 489 SILKVVINN Nucleic acid helicase Q8IWW2 DDXx 490 LLYGGDLHSA Nucleic acid helicase Q8IWW2 DDXx 491 KLAENIDAQL Nucleoporin 62 kDa Q6GTM2 (NUP62 protein) 492 SLLTDEEDVD Nuclear pore complex P52948 protein Nup98-Nup96 precursor [Contains: Nuclear pore complex protein Nup98 (Nucleo- porin Nup98) (98 kDa nucleoporin); 493 VDITQEPVL Nuclear pore complex P52948 protein Nup98-Nup96 precursor [Contains: Nuclear pore complex protein Nup98 (Nucleo- porin Nup98) (98 kDa nucleoporin); 494 QLEKKLME Nucleoprotein TPR P12270 495 GLDPLGYEIQ Nuclear pore complex P57740 protein Nup107 496 ALLDRIVSV Nuclear pore complex Q92621 protein Nup205 497 KILDLETQL ODF2 protein Q6PJQ8 498 VTWLKETEV Trophoblast glycopro- Q6PJQ8 tein precursor (5T4 oncofetal trophoblast glycoprotein) 499 VDLPGVINTV Dynamin-like 120 kDa O60313 protein, mitochondrial precursor (Optic atrophy 1 gene protein) 500 TITCLPATLV Orexin receptor type 2 O43614 (Ox2r) (Hypocretin receptor type 2) 501 LLGPRLVLA Transmembrane emp24 do- P49755 main-containing protein 10 precursor (Transmem- brane protein Tmp21) 502 LTTPDAAGVNQ Orphan nuclear receptor P13056 TR2 (Testicular receptor 2) 503 FLDGHDLQL MKL/myocardin-like pro- Q969V6 tein 1 (Myocardin-re- lated transcription factor A) (MRTF-A) (Megakaryoblastic leukemia 1 protein) (Megacaryocytic acute leukemia protein) 504 KTTEVLDASA Ovarian cancer related Q8WXI7 tumor marker CA125- 505 TSPTVPWTTSIF Ovarian cancer related Q8WXI7 tumor marker CA125- 506 WTITDTTEH Ovarian cancer related Q8WXI7 tumor marker CA125- 507 TITNLQYGE Ovarian cancer related Q8WXI7 tumor marker CA125- 508 ARLTFLNRG Oxysterol-binding pro- Q9BZF1 tein-related protein 8 (OSBP-related protein 8) 509 KIDALSSEKL Centrosomal protein of Q8NHQ1 70 kDa (Cep70 protein) (p10-binding protein) 510 LLAEAVLTYL Leucine carboxyl O60294 methyltransferase 2 (EC 2.1.1.-) (p21WAF1/CIP1 promoter-interacting protein) 511 SLFEKGLKNV F-box/LRR-repeat pro- Q9UKA1 tein 5 (F-box and leu- cine-rich repeat pro- tein 5) (F-box protein FBL4/FBL5) 512 LDTPSQPVNN Inhibitor of growth Q9NXR8 protein 3 513 VLDELKNMKC P53 inducible protein Q9UN29 514 PQDYPDKKSLP DNA polymerase alpha P09884 catalytic subunit (EC 2.7.7.7) 515 NLLPKLHIV Chloride intracellular Q9Y696 channel protein 4 (In- tracellular chloride ion channel protein p64H1 516 LAAAGGPGQGWA Paired mesoderm homeo- Q99453 box protein 2B (Paired- like homeobox 2B) (PHOX2B homeodomain protein) (Neuroblastoma Phox) 517 GTPPPPGKPE PRB3 protein P81489 518 SQGAVGLAGV Protein patched homolog Q13635 1 (PTC1) (PTC) 519 ELKKINYQV Protein patched homolog Q13635 1 (PTC1) (PTC) 520 KLFQDLQDL Rap guanine nucleotide Q9Y4G8 exchange factor 2 (Neural RAP guanine nu- cleotide exchange pro- tein) (nRap GEP) (PDZ domain-containing gua- nine nucleotide ex- change factor 1) (PDZ- GEF1) 521 EAIVSHEKN Pecanex-like protein 1 Q96RV3 (Pecanex homolog) 522 GLLPQVNTFV Pecanex-like protein 1 Q96RV3 (Pecanex homolog)- 523 KAYDVEREL GC-1-related estrogen Q8TDE4 receptor alpha coacti- vator short isoform 524 DVLESWLDF PHD finger Q86U89 525 TMLVLVIRG Hypothetical protein Q6N038 DKFZp686C07187 526 DVAQLQALLQ Phosphatidylinositol- P42338 4,5-bisphosphate 3-ki- nase catalytic subunit beta isoform (EC 2.7.1.153) (P13-kinase p110 subunit beta) (PtdIns-3-kinase p110) 527 QIIEANYHS Phosphodiesterase 8A, Q6P9H3 isoform 1 528 YVTDVLYRV Serine/threonine-pro- Q96Q15 tein kinase SMG1 (EC 2.7.11.1) (SMG-1) (hSMG-1) (Lambda/iota protein kinase C-in- teracting protein) (Lambda-interacting protein) ( 529 FLDDEVIEL PiggyBac transposable Q8N328 element derived 3 530 VICILPNDDK PIWIL3 protein Q7Z3Z3 531 IQNSQLQLQ Homeobox protein PKNOX1 P55347 (PBX/knotted homeobox 1) 532 FAYLLTYMA Transmembrane protein Q12893 115 (Protein PL6) 533 GLIDSLVHYV Plakophilin-2 Q99959 534 REDHPARP Plectin 6 Q6S380 535 FLLDPVKGERL Plectin 1 (PLTN) (PCN) Q15149 (Hemidesmosomal protein 1) (HD1) 536 RGQNLDVVQ Plexin B1; plexin 5; O43157 semaphorin receptor 537 SLTGHISTV Pleiotropic regulator 1 O43660 538 EPLRVPPDL Blood vessel epicardial Q8NE79 substance (hBVES) (Pop- eye domain-containing protein 1) (Popeye protein 1) 539 EIPVLNELPV Carboxypeptidase-like Q8N436 protein X2 precursor 540 LYIPAMAFI YIF1B protein YIF1B protein 541 SLLQHLIGL Melanoma antigen pre- P78395 ferentially expressed in tumors (Pr4eferen- tially expressed anti- gen of melanoma) (OPA- interacting protein 4) 542 ISSMLVLFF Splice isoform 2 of Q9H7F0-2 Q9H7F0 543 ENHSSQTDNI P2Y purinoceptor 13 Q9BPV8 (P2Y13) (G-protein coupled receptor 86) (G-protein coupled receptor 94) 544 ILMGVLKEV Putative pre-mRNA- O43143 splicing factor ATP- dependent RNA helicase DHX15 (EC 3.6.1.-) (DEAH box protein 15) (ATP-dependent RNA helicase #46) 545 VLFENTDSVHL HUMAN RNA-binding pro- P42696 tein 34 (RNA-binding motif protein 34) 546 INMRIQDL Prolyl 4-hydroxylase P13674 alpha-1 subunit precur- sor (EC 1.14.11.2) (4- PH alpha-1) (Procolla- gen-proline,2-oxoglu- tarate-4-dioxygenase alpha-1 subunit) 547 KTDKTLVLL Profilin-1 P07737 548 GLIEILKKV Programmed cell death O14737 protein 5 (TFAR19 pro- tein) (IF-1 cell apop- tosis-related gene 19 protein) 549 NMVDIIHSV Propionyl-CoA carboxy- P05166 lase beta chain, mito- chondrial precursor (EC 6.4.1.3) 550 ILDAGGHNVTI 26S proteasome non- Q99460 ATPase regulatory sub- unit 1 (26S proteasome regulatory subunit RPN2) (26S proteasome regulatory subunit S1) (26S proteasome subunit p1112) 551 YMNLEKPDFI 26S proteasome non- Q99460 ATPase regulatory sub- unit 1 (26S proteasome regulatory subunit RPN2) (26S proteasome regulatory subunit S1) (26S proteasome subunit p112) 552 SLADIAQKL 26S proteasome non- O43242 ATPase regulatory sub- unit 3 (26S proteasome regulatory subunit S3) (Proteasome subunit p58) 553 QLVDIIEKV Proteasome activator P61289 complex subunit 3 (Pro- teasome activator 28- gamma subunit) (PA28gamma) (PA28g) (Activator of multi- catalytic protease sub- unit 3) (11S regulator complex gamma subunit) (REG-gamma) (Ki nuclear autoantigen) 554 SLLKVDQEV Proteasome activator P61289 complex subunit 3 (Pro- teasome activator 28- gamma subunit) (PA28gamma) (PA28g) (Activator of multi- catalytic protease sub- unit 3) (11S regulator complex gamma subunit) (REG-gamma) (Ki nuclear autoantigen) 555 QILRLLHIE Protein C14orf166 Q9Y224 556 EMGGGENNLK Protein KIAA1219 Q86X10 557 NLAEKLIGV Protein KIAA1219 Q86X10 558 EKSVSVQTNL Protein KIAA1688 Q9COH5 559 GLLDSLTGILN Protein Plunc precursor Q9NP55 (Palate lung and nasal epithelium clone pro- tein) (Lung-specific protein X) (Nasopharyn- geal carcinoma-related protein) (Tracheal epi- thelium-enriched pro- tein) (Secretory pro- tein in upper respira- tory tracts) 560 SLLPPDALVGL Protein transport pro- Q15437 tein Sec23B 561 LEEKNTLIQEL Liprin-alpha-2 (Protein O75334 tyrosine phosphatase receptor type f poly- peptide-interacting protein alpha-2) (PTPRF-interacting protein alpha-2) 562 LLSESNERL Liprin-alpha-2 (Protein O75334 tyrosine phosphatase receptor type f poly- peptide-interacting protein alpha-2) (PTPRF-interacting protein alpha-2) 563 LADLGSLESP Protocadherin gamma A12 O60330 precursor (PCDH-gamma- A12) (Cadherin-21) (Fibroblast cadherin 3) 564 QLLKFQLNK Protocadherin gamma A10 Q9Y5H3 precursor (PCDH-gamma- A10) 565 LLAEAVLTYL Leucine carboxyl O60294 methyltransferase 2 (EC 2.1.1.-) (p21WAF1/ CIP1 promoter-interact- ing protein) 566 QLLREPHLQ KIAA1636 protein Q9HCD6 567 TIPNLEQIE Probable G-protein Q9UJ42 coupled receptor 160 568 KLWEAESKL Protein C21orf45 Q9NYP9 569 IFHLHELPE Periodic tryptophan Q15269 protein 2 homolog 570 KLFNDAIRL Rab-like protein 2B Q9UNT1 571 FENQEVQAI Cell cycle checkpoint O75943 protein RAD17 (hRad17) (RF-C/activator 1 homolog) 572 EYVEKFYRI DNA repair protein Q92878 RAD50 (EC 3.6.-.-) (hRAD50) 573 QIDEIRDK DNA repair protein Q92878 RAD50 (EC 3.6.-.-) (hRAD50) 574 FLHEKLESL Ras GTPase-activating P20936 protein 1 (GTPase-acti- vating protein) (GAP) (Ras p21 protein acti- vator) (p120GAP) (RasGAP) 575 FELNNELKM Ras guanine nucleotide Q9UK56 exchange factor 2 576 LLSNNNQAL Ras-GTPase-activating Q13283 protein-binding protein 1 (EC 3.6.1.-) (ATP- dependent DNA helicase VIII) (GAP SH3-domain- binding protein 1) (G3BP-1) (HDH-VIII) 577 VLCGNKSDLE Ras-related protein P51159 Rab-27A (Rab-27) (GTP- binding protein Ram) 578 LLMYDIAN Ras-related protein O95716 Rab-3D 579 SQVNILSKIVSR Nuclear pore complex P57740 protein Nup107 (Nucleo- porin Nup107) (107 kDa nucleoporin) 580 VMFNGKVYL Receptor-interacting Q86XS4 factor 1 581 LEVEVIEAR Regulating synaptic Q9UJD0 membrane exocytosis protein 3 (Nim3) (Rab-3 interacting molecule 3) (RIM 3) (RIM3 gamma) 582 TLLRGIEW Regulator of G protein Q86UV0 signaling protein (Reg- ulator of G-protein signalling like 1) 583 PDFTELDLQ MHC class II regulatory P22670 factor RFX1 (RFX) (En- hancer factor C) (EF-C) 584 DVLFALFSKL Retinoblastoma-associa- P06400 ted protein (PP110) (P105-RB) 585 RSGERKAVQA Roundabout homolog 3 Q96MS0 precursor (Roundabout- like protein 3) 586 GLNEEIARV Retinoblastoma-associa- O14777 ted protein HEC (Kine- tochore associated 2) 587 FLFQEPRSI Retinoblastoma-associa- Q9UK61 ted protein RAP140 588 FLFQEPRSIVT Retinoblastoma-associa- Q9UK61 ted protein RAP140 589 KEVDILNLP AT-rich interactive do- P29374 main-containing protein 4A (ARID domain-con- taining protein 4A) (Retinoblastoma-binding protein 1) 590 YKLPMEDLK Jumonji/ARID domain- P29375 containing protein 1A (Retinoblastoma-binding protein 2) (RBBP-2) 591 TMVDRIEEV Jumonji/ARID domain- P29375 containing protein 1A (Retinoblastoma-binding protein 2) (RBBP-2) 592 VEGLLTLSDFDL RhoGTPase regulating Q6RJU5 protein variant ARHGAP20-lad 593 WMLDKLTGV 405 ribosomal protein Q8TD47 S4, Y isoform 2 594 LLKHLLLLL RNA binding motif Q13380 595 ALLSRLEQI RNA binding protein Q2M365 (Autoantigenic, hnRNP- associated with lethal yellow), long isoform- 596 DVYEDELVP RNA-binding protein Q8NI52 597 VMLGGRNIKV Ro ribonucleoprotein- Q9UHX1 binding protein 1 (SIAHBP1 protein) 598 RLDELGGVYL HUMAN QSJYR6 OTTHUMP00000030902 599 FEDKLIEDL Ryanodine receptor 2 Q92736 (Cardiac muscle-type ryanodine receptor) (RyR2) (RYR-2) (Cardiac muscle ryanodine recep- tor-calcium release channel) (hRYR-2) 600 QLIDKVWQL SEC14-like protein 1 Q92503 601 FLLEPQMKV Secreted and transmem- Q8WVN6 brane protein 1 pre- cursor (Protein K12) 602 ILNEDGSPNL Neudesin precursor Q9UMX5 (Neuron-derived neuro- trophic factor) 603 LLAILILAL P-selectin glycoprotein Q14242 ligand 1 precursor (PSGL-1) (Selectin P ligand) (CD162 antigen) 604 SMNRGGYMP Semaphorin-6D precursor Q8NFY4 605 EFIDGSLQM Serine/threonine/tyro- Q8WUJ0 sine-interacting pro- tein (Protein tyrosine phosphatase-like protein) 606 ILVVYVIGL Olfactory receptor 8G5 Q8NG78 (Olfactory receptor OR11-298) 607 TLSERLWLG Shb-like adapter Q7M4L6 protein, Shf 608 VLWDRTFSL Signal transducer and P42224 activator of transcrip- tion 1 -alpha/beta (Transcription factor ISGF-3 components p91/p84) STAT1 609 NVNFFTKPP Signal transducer and P40763 activator of transcrip- tion 3 (Acute-phase response factor) 610 ETFSGVYKK 40S ribosomal protein P62081 S7 611 QLDDLKVEL 60S ribosomal protein P42766 L35 612 MEDLIHEI 60S ribosomal protein P18124 L7 613 QTDVDNDLV Thrombospondin-2 P35442 precursor 614 LLIDPPRYI C3 and PZP-like alpha- Q8IZJ3 2-macroglobulin domain containing 8 615 PSIPTSAQHV C3 and PZP-like alpha- Q8IZJ3 2-macroglobulin domain containing 8 616 FLDEPTNHL ATP-binding cassette Q9UG63 sub-family F member 2 (Iron-inhibited ABC transporter 2) 617 KMDDPDYWRTV Ribosome biogenesis Q14137 protein BOP1 (Block of proliferation 1 protein) 618 LANVQQVQI CDNA FLJ13765 fis, Q9H8C5 clone PLACE4000128, weakly similar, to Mus musculus putative transcription factor mRNA 619 SLFVVILVT GD200 cell surface Q6Q8B3 glycoprotein receptor isoform 2 variant 2 620 ARTIKIRNI LRRC58 protein Q96CX6 621 LVLTSGIVFV Claudin-6 (Skullin 2) P56747 622 VISFDKLKL T-box transcription O95935 factor TBX18 (T-box protein 18) 623 DLMELYKV INTS7 protein Q8WUH5 624 LQRRKPTGAF FRAS1-related extracel- Q5SZK8 lular matrix protein 2 precursor (ECM3 homolog) 625 KVNNEKFRT Zinc finger protein 318 Q5VUA4 (Endocrine regulatory protein) 626 SLDQPTQTV Eukaryotic translation Q99613 initiation factor 3 subunit 8 (eIF3 p110) (eIF3c) 627 SVTSEGIKAV HUMAN LOC196394 protein Q81Y45 628 ISLSEPAKPG Hypothetical protein Q8NDZ2 FLJ44216 629 ILDKKVEKV Heat shock protein HSP P08238 90-beta (HSP 84) (HSP 90) 630 KLSAEVESLK Sarcoma antigen NY-SAR- Q5T9S5 41 (NY-SAR-41) 631 VTWDAALYI Protein FAM86A Q96G04 632 YLLPKDIKL Ras-like family 11 Q6T310 member A (OTTHUMP00000018162) 633 RLLEDGEDFNL Keratin, type I cyto- P05783 skeletal 18 (Cytokera- tin-18) (CK-18) 634 RVLPYPFTH U3 small nucleolar RNA- Q9BVJ6 associated protein 14 homolog A (Antigen NY- CO-16) 635 QNQERLER Hypothetical protein Q68DM0 DKFZp781D1722 636 QDNIKELEL Chromosome-associated O95239 kinesin KIF4A (Chromokinesin) 637 ILKQRDNEI Kinesin-like protein Q6ZMV9 KIF6 638 QNELDNVSTL Myosin-10 (Myosin heavy P35580 chain, nonmuscle IIb) (Nonmuscle myosin heavy chain IIb) 639 NIDLLDDGSN Hypothetical protein Q8IY85 C17orf57 640 VLQSNIQHV Similar to peptide N- Q9BVR8 glycanase homolog (S.cerevisiae) 641 VFFDIAVDGEPL Peptidyl-prolyl cis- P62937 trans isomerase A (EC 5.2.1.8) 642 DFHFPKFSI Serpin A13 precursor Q6UXR4 643 SYVNLPTIAL 40S ribosomal protein P08865 SA (p40) (34/67 kDa laminin receptor) (Colon carcinoma laminin-binding pro- tein) (NEM/1CHD4) (Mul- tidrug resistance-as- sociated protein MGr1- Ag) 644 SNLEHLGHE N-acetylglucosamine-1- Q9UJJ9 phosphotransferase sub- unit gamma precursor 645 LKLKLTAVEK Liprin-beta-1 (Protein Q86W92 tyrosine phosphatase receptor type f poly- peptide-interacting protein-binding protein 1) 646 GLKGRVFEV 40S ribosomal protein P61247 S3a 647 SLADLQNDEV 40S ribosomal protein P61247 S3a 648 NNLPHLQVV L0C124512 protein Q86XA0 (Fragment) 649 ISFGGSVQL Hypothetical protein Q96KX1 MGC26744 650 SILDQILQ Hypothetical protein Q96KW9 L0C122258 651 TLSDLRVYL Sulfiredoxin-1 (EC Q9BYN0 1.8.98.2) 652 EAFVNSKN Basalin Q5QJ38 653 VTWDAALYL Protein FAM86A Q96G04 654 VLDDKLVFV Transmembrane protein Q4KMQ2 16F 655 YLLDLHSYL TEB4 protein O14670 656 FLALAVIQL SLC10A5 Q5PT55 657 TLAEVSTRL Serine/threonine-pro- P57059 tein kinase SNF1-like kinase 1 (EC 2.7.11.1) 658 VIEVYQEQI L0C391257 protein Q6P094 659 RLWEEAVKA Zinc finger protein 161 Q14119 (Putative transcription factor DB1) 660 SLKTLMLR Slit homolog 2 protein O94813 precursor(Slit-2) 661 EIKKKFKL FYN-binding protein O15117 (FYN-T-binding protein) 662 VHKEMFIMV Jumonji/ARID domain- P41229 containing protein 1C (SmcX protein) (Xe169 protein) 663 VHKEMFIMV Jumonji/ARID domain- Q9BY66 containing protein 1D (SmcY protein) (Histo- compatibility Y antigen) 664 LAGSEVALAGV Monocarboxylate trans- O95907 porter 3 (MCT 3) 665 IPHDLFTEL Solute carrier family 4 Q6U841 sodium bicarbonate cotransporter-like member 10- 666 FLADPDTVNHLL Sorting nexin 14, iso- Q6NUI7 form a 667 RVADRLYGV Sorting nexin-4 O95219 668 HRPDLLDY Spectrin beta chain, Q9NRC6 brain 4 (Spectrin, non- erythroid beta chain 4) 669 TLDENHPSI Spermatogenesis-assoc- Q9P0W8 iated protein 7 (Sperm- atogenesis-associated protein HSD3) 670 TLAEIAKVEL Non-POU domain-contain- Q15233 ing octamer-binding protein (NonO protein) (54 kDa nuclear RNA- and DNA-binding pro- tein) (p54(nrb)) (p54nrb) (55 kDa nuclear protein) 671 DVAVEAIRL Cohesin subunit SA-1 Q8WVM7 (Stromal antigen 1) (SCC3 homolog 1) 672 LMVDHVTEV Steroid receptor RNA Q9HD15 activator isoform 1 673 SLYEMVSRV Structure-specific Q08945 recognition protein 1 (SSRP1) (Recombination signal sequence recog- nition protein) (T160) (Chromatin-specific transcription elonga- tion factor 80 kDa subunit) 674 SINPKRAKL Suppressor of hairy Q86YH2 wing homolog 2 (5′OY11.1) (Zinc finger protein 632) 675 NMYGKVVTV Transcription elonga- O00267 tion factor SPT5 (hSPT5) (DRB sensitiv- ity-inducing factor large subunit) (DSIF large subunit) (DSIF p160) (Tat-cotransacti- vator 1 protein) (Tat- CT1 protein)- 676 SLFATEQL Synaptogyrin-3 O43761 677 RLQEGDKILSV Synaptojanin-2-binding P57105 protein (Mitochondrial outer membrane protein 25) 678 AMFDKKVQL Synemin Q8TE61 679 ALNELLQHV Talin-1 Q9Y490 680 RVVSMAALAM TAR RNA loop binding v protein (TAR (HIV) RNA binding protein 1) 681 GIIMQIIDV Taste receptor type 2 Q9NYW6 member 3 (T2R3) 682 IFNAIALFL Taste receptor type 2 P59535 member 40 (T2R40) (T2R58) (G-protein coupled receptor 60) 683 LEQGLFSKV Oxidoreductase HTATIP2 Q9BUP3 (EC 1.1.1.-) (HIV-1 TAT-interactive protein 2) 684 KFMHMGKRQK Transcription initia- P49848 tion factor TFIID sub- unit 6 (Transcription initiation factor TFIID 70 kDa subunit) (TAF(II)70) (TAFII-70) (TAFII-80) (TAFII80) 685 SNFGNEKL TRA@ protein Q6PIP7 686 FLLDKKIGV T-complex protein 1 P78371 subunit beta (TCP-1- beta) (CCT-beta) 687 RSLAASNPIL Telomerase-binding Q86U58 protein EST1A (Ever shorter telomeres 1A) (Telomerase subunit EST1A) (EST1-like pro- tein A) (hSmg5/7a) 688 EMESLTGHQ Tumor endothelial mar- Q96PE0 ker 6 (Hypothetical protein TEM6) 689 LDFQEELEV Ras GTPase-activating- Q13576 like protein IQGAP2 690 SPNSEGDAGDL Tetratricopeptide re- Q8WVT3 peat protein 15 (TPR repeat protein 15) 691 LVYLNESSVLH Myosin-18A (Myosin Q92614 XVIIIa) (Myosin con- taining PDZ domain) (Molecule associated with JAK3 N-terminus) (MAJN) 692 VAGIKVNQVK Polycystic kidney and Q8TCZ9 hepatic disease 1 pre- cursor (Fibrocystin) 693 ILYELQVEL TMC4 protein Q7Z5M3 694 EVLDELYRV MDC-3.13 isoform 1 Q9UER5 (TNFAIP8 protein) 695 TNIEDGVFET Toll-like receptor 8 Toll- precursor like receptor 8 pre- cursor 696 EIRKNEGQI Tolloid-like protein 1 O43897 precursor (EC 3.4.24.-) 697 IAAKILSYN DNA topoisomerase I, Q969P6 mitochondrial precursor (EC 5.99.1.2) (TOP1mt) 698 LYGRHFNYL PAP associated domain- Q8NDF8 containing protein 5 (EC 2.7.7.-) (Topoisomerase-related function protein 4-2) (TRF4-2) 699 NLFNKYPAL Plastin-3 (T-plastin) P13797 700 YLDEIVKEV Translocated promoter Q5SWY0 region (To activated MET oncogene) 701 ENHSSQTDNI P2Y purinoceptor 13 Q9BPV8 (P2Y13) (G-protein coupled receptor 86) (G-protein coupled re- ceptor 94) 702 RTHMLSSL Transcript Y 5 Q9BXH6 703 QATIAPVTV Transcription factor Q02446 Sp4 (SPR-1) 704 NLFRAPIYL Transcription initia- P21675 tion factor TFIID sub- unit 1 (EC 2.7.11.1) (Transcription initia- tion factor TFIID 250 kDa subunit) (TAF(II)250) (TAFII- 250) (TAFII250) (TBP- associated factor 250 kDa) (p250) (Cell cycle gene 1 protein) 705 KLEEEQEKNQL Transcriptional repres- Q8NI51 sor CTCFL (CCCTC-bind- ing factor) (Brother of the regulator of im- printed sites) (Zinc finger protein CTCF-T) (CTCF paralog 706 LNVDTPFPL Transducer of regulated Q6UUV7 CREB protein 3 707 ILYELKVEL Transmembrane channel- Q7Z404 like protein 4 708 KFMHMGKRQK Transcription initia- P49848 tion factor TFIID sub- unit 6 (Transcription initiation factor TFIID 70 kDa subunit) (TAF(II)70) (TAFII-70) (TAFII-80) (TAFII80) 709 HSDEGGVASL Trophinin-associated Q12815 protein (Tastin) (Tro- phinin-assisting protein) 710 AMLTGELKKA Tryptophanyl-tRNA syn- P23381 thetase (EC 6.1.1.2) (Tryptophan--tRNA ligase) (TrpRS) (IFP53) (hWRS) 711 VFPTHVFPT Tubulin, gamma complex Q5T9Y2 associated protein 3 712 KELAELRESTS Tumor necrosis factor P48023 ligand superfamily member 6 (Fas antigen ligand) (Fas ligand) (CD178 antigen) (CD95L protein) (Apoptosis antigen ligand) (APTL) [Contains: Tumor necro- sis factor ligand superfamily member 6, membrane form 713 LTDKEGWIL Tumor necrosis factor, Q13829 alpha-induced protein 1, endothelial (B12 protein) 714 VVTYKNENI Netrin receptor DCC P43146 precursor (Tumor sup- pressor protein DCC) (Colorectal cancer suppressor) 715 TVAEGLIED Adipocyte-derived leu- Q9NZ08 cine aminopeptidase precursor (EC 3.4.11.-) (A-LAP) (ARTS-1) (Aminopeptidase PILS) (Puromycin-insensitive leucyl-specific amino- peptidase) (PILS-AP) (Type 1 tumor necrosis factor receptor shedding aminopeptidase 716 NEKIKKDEL U1 small nuclear ribo- P09012 nucleoprotein A (U1 snRNP protein A) (U1A protein) (U1-A 717 ILDESHERV U6 snRNA-associated O95777 Sm-like protein LSm8 718 NLYSDYILN Ubiquitin-protein Q05086 ligase E3A (EC 6.3.2.-) (E6AP ubiquitin-protein ligase) (Oncogenic pro- tein-associated protein E6-AP) (Human papillo- mavirus E6-associated protein) 719 RYVNGHAK Ubiquitin carboxyl- Q9Y6I4 terminal hydrolase 3 (EC 3.1.2.15) (Ubiqui- tin thioesterase 3) (Ubiquitin-specific- processing protease 3) (Deubiquitinating en- zyme 3) 720 KLLDLELAPS UBX domain-containing Q92575 protein 2 721 YLYDLNHTL UNC93 homolog B1 (UNC- Q9H1C4 93B protein) (hUNC93B1) 722 FFFWLMEL Splice isoform 5 of Q9H171-5 Q9H171 723 ELSSLKETHI CDNA FLJ46282 fis, Q6ZRK6 clone TESTI4031066 724 KLGSVPVTV CCDC73 protein Q6P5Q7 725 ALWERIEGV Caspase recruitment do- Q9BWT7 main-containing protein 10 (CARD-containing MAGUK protein 3) (Carma 3) 726 VKAQEILR Caspase recruitment do- Q9BWT7 main-containing protein 10 (CARD-containing MAGUK protein 3) (Carma 3) 727 ANVDAIVVSV Chromatin-specific Q9Y5B9 transcription elonga- tion factor FACT 140 kDa subunit 728 CKDGEDSIIR Beta-defensin 120 Q8N689 precursor 729 DNTKKSDKT Alpha-catulin (Catenin Q9UBT7 alpha-like protein 1) (Alpha-catenin-related protein) 730 EFLGDSIMQ Ribonuclease III (EC Q9NRR4 3.1.26.3) (RNase III) 731 EFLQEGLEK Seizure related 6 Q53EL9 homolog 732 FLLKCLEQV Granulocyte colony- P09919 stimulating factor precursor (G-CSF) (Pluripoietin) (Fil- grastim) (Lenograstim) 733 FLTDSNNIKEV Lysyl-tRNA synthetase Q9HB23 734 GGVQELLNQQ Protein C6orf130 Q9Y530 735 GKPRRKSNL Melanophilin (Exo- Q9BV36 philin-3) (Synaptotag- min-like protein 2a) (Slp homolog lacking C2 domains a) 736 HIKEELMHG Novel protein (Possible Q5VTR6 ortholog of mouse phos- phoinositide-3-kinase adaptor protein 1 (Pik3ap1) 737 HIPFFLHN AER61 glycosyltrans- Q6P985 ferase 738 ILEKKVEKV Heat shock protein HSP P07900 90-alpha (HSP 86) 739 ILMEHIHKL 60S ribosomal protein P84098 L19 740 KASQLGIFISKV PDZ domain-containing Q5EBL8 protein 11 741 KILEVMHTK Dedicator of cytokine- Q5JSL3 sis 11-; Cdc42-associa- ted guanine nucleotide exchange factor ACG/DOCK11 742 LAVGTSPVLA Hypothetical protein Q6ZNX6 FLJ26930 743 LLAEEARKL Laminin gamma-1 chain P11047 precursor (Laminin B2 chain) 744 LLGICFCIA ATP-binding cassette Q96J66 transporter sub-family C member 11 (Multidrug resistance-associated protein 8) 745 LMAEMGVHSV Uridine/cytidine Q9NWZ5 kinase-like 1 746 ISRLENITV Butyrophilin-like pro- Q6UX41 tein 8 precursor 747 MISLPGPLVTN Endothelial cell- Q96AP7 selective adhesion molecule precursor 748 MLLDVMHTV Poly(A)-specific ribo- O95453 nuclease PARN (EC 3.1.13.4) (Polyadenyl- ate-specific ribonucle- ase) (Deadenylating nu- clease) (Deadenylation nuclease) 749 NVMNLIDFV Voltage-gated potassium Q96RP8 channel KCNA7 750 NVTMKDNKI F-box protein 11 Q52ZP1 751 PRSNIDVNI rythrocyte membrane Q7Z5S1 protein band 4.1 like 5 752 PSAQPLLSL CDNA FLJ45015 fis, Q6ZT30 clone BRAWH3014639 753 QLKESKLKI FAM13A1_v2 protein Q24JP0 754 RDAPHLPDG Hypothetical protein Q6ZP70 FLJ26432 755 RLPPEGILHNV VPS13D-1A protein Q709C5 756 SEGAEYDDQT Coagulation factor VIII P00451 precursor (Procoagulant component) (Antihemo- philic factor) (AHF) 757 SLFERLVKV NFX1-type zinc finger- Q9P2E3 containing protein 1 758 SLLDKIIGA Polymerase I and trans- Q6NZI2 cript release factor (PTRF protein) 759 SMMDVDHQI T-complex protein 1 P48643 subunit epsilon (TCP-1- epsilon) (CCT-epsilon) 760 TLDEKIEKV Probable ATP-dependent Q96GQ7 RNA helicase DDX27 (EC 3.6.1.-) (DEAD box protein 27) 761 TLLEDGTFKV HSCARG Q9HBL8 762 TVLKTKFSS CDNA FLJ43956 fis, Q6ZU72 clone TESTI4015681 763 VIFEDVGRQVL Mitochondrial-process- Q10713 ing peptidase alpha subunit, mitochondrial precursor (EC 3.4.24.64) (Alpha-MPP) 764 YILDINPLL CDNA FLJ45287 fis, Q6ZSR0 clone BRHIP3002124 765 YKTFSTSMMLL Hypothetical protein Q96I36 C12orf62 766 RLPPEGILHNV VPS13D-2A protein Q709C4 767 LLGPRVLSP CDNA FLJ32009 fis, Q96DN2 clone NT2RP7009498, weakly similar to FIBULIN-1, ISOFORM A 768 FIILLVTYI Transient receptor po- Q9HBA0 tential cation channel subfamily V member 4 (TrpV4) (osm-9-like TRP channel 4) (OTRPC4) (Vanilloid receptor- like channel 2) (Vanilloid receptor- like protein 2) (VRL-2) 769 FYDIEILK Vascular endothelial O43915 growth factor D precur- sor (VEGF-D) (c-fos- induced growth factor) (FIGF) 770 WMAPESIFDKI Vascular endothelial P17948 growth factor receptor 1 precursor (EC 2.7.10.1) (VEGFR-1) (Vascular permeability factor receptor) (Tyro- sine-protein kinase re- ceptor FLT) (Flt-1) (Tyrosine-protein kinase FRT) (Fms-like tyrosine kinase 1) 771 LLDQQNPDE Proto-oncogene C-crk P46108 (P38) (Adapter molecule crk) 772 VMFKKIKSFEV VDUP1 protein (Thiore- Q9H3M7 doxin interacting protein) 773 KLLEGEESRISL Vimentin P08670 774 KLLEGEESRISL HUMAN CTCL tumor anti- Q548L2 gen HD-CL-06 (Vimentin variant) 775 RILGAVAKV Vinculin (Metavinculin) P18206 776 SLSMVNHRL Integrin alpha-3 pre- P26006 cursor (Galactoprotein B3) (GAPB3) (VLA-3 alpha chain) (FRP-2) (CD49c antigen) [Con- tains: Integrin alpha-3 heavy chain; Integrin alpha-3 light chain] 777 VGQADGGLSVLR Voltage-dependent T- O95180 type calcium channel alpha-1H subunit (Vol- tage-gated calcium channel alpha subunit Cav3.2) (Low-voltage- activated calcium channel alphal 3.2 subunit) 778 DVATILSRR Wiskott-Aldrich syn- Q8IV90 drome protein family member 4 (WASP-family protein member 4) 779 PKFEVIEKPQA ATP synthase coupling P18859 factor 6, mitochondrial precursor (EC 3.6.3.14) (ATPase subunit F6) 780 NCTTIDDSLAI Proto-oncogene protein P56703 Wnt-3 precursor 781 ILPIVILAN myloid beta A4 precur- Q99767 sor protein-binding family A member 2 (Neuron-specific X11L protein) (Neuronal Munc 18-1-interacting protein 2) (Mint-2) (Adapter protein X11 beta) 782 EFLELSAAQE Zinc finger CCHC do- Q8N8U3 main-containing protein 5 783 SLTDKVQEA Myeloidl/ymphoid or Q59FF2 mixed-lineage leukemia (Trithorax homolog, Drosophila) variant 784 SKNSALEYQL Zinc finger protein Q86YF9 DZIP1 (DAZ-interacting protein 1/2) 785 LQDVEEVEI Hypothetical protein Q69YS5 DKFZp761O1618 786 FLDEPTNHL ATP-binding cassette Q9UG63 sub-family F member 2 (Iron-inhibited ABC transporter 2) 787 KMDDPDYWRTV Ribosome biogenesis Q14137 protein BOP1 (Block of proliferation 1 protein) 788 LANVQQVQI CDNA FLJ13765 fis, Q9H8C5 clone PLACE4000128 789 KLDPTKTTL NDRG1 protein (N-myc Q92597 downstream regulated gene 1 protein) 790 HLTYLNVYL Pre-mRNA splicing Q92620 factor ATP-dependent RNA helicase PRP16 791 ALWDKLFNL Nesprin 2 (Nuclear en- Q9NU50 velope spectrin repeat protein 2) 1514 KIMDQVQQA Adenomatous polyposis P25054 coli 1515 RLQEDPPAGV Ubiquitin conjugating P49459 enzyme E2 1516 KLDVGNAEV B cell receptor- P5572 associated protein BAP31 (CDM protein) 6c6-AG 1517 FLYDDNQRV Topoisomerase Il-alpha P11388 1518 FLYDDNQRV Topoisomerase II beta Q02880 1519 ALMEQQHYV Integrin beta8 subunit P26012 precursor 1520 YLMDTSGKV Replication Protein A P27694 1521 ILDDIGHGV Abl Binding protein 3 U31089 1522 LLDRFLATV Cyclin I Q14094 1523 LLIDDKGTIKL Cell Division Control P06493 Protein 2 (CDC2) 1524 RLYPWGVVEV Septin 2 (NEDD5) Q15019 1525 KLQELNYNL STAT1 alpha/beta P42224 1526 ILIEHLYGL LDL Receptor-related Q07954 protein (LRP) 1527 YLIELIDRV TACE (ADAM17) NP- 068604 1528 NLMEQPIKV Junction plakoglobin P14923 (gamma catenin) 1529 FLAEDALNTV EDDR1 Q08345 1530 TLLNVIKSV IP3 receptor type II Q14571 1531 MLKDIIKEY Melanoma-associated Q9UNF1 antigen D2 (MAGE-D2 antigen) (MAGE-D) (Breast cancer-associ- ated gene 1 protein) (BCG-1) (11B6) (Hepato- cellular carcinoma-as- sociated protein JCL-1) 1532 TSYVKVLEH Melanoma-associated P43358 antigen 4 (MAGE-4 anti gen) (MAGE-X2) (MAGE-41) 1533 HEYLKAFKV HUMAN Retinoblastoma- Q08999 like protein 2 (130 kDa retinoblastoma- associated protein) (PRB2) (P130) (RBR-2)

TABLE 3 SEQ ID NO, Parent Protein Identification and SwissProt Identification Number for full-length sequences 792-1513 Parent SEQ SwissProt ID Identification NO: Parent Sequence Identification No. 792 BCL-6 corepressor long isoform_(—) Q6W2J9 793 E1B_19K/Bcl-2-interacting protein Nip3 Q12983 794 Similar to Heat shock protein HSP 90-beta (HSP 84) (HSP P08238 90) 795 Cytochrome P450 11B2, mitochondrial precursor P19099 796 2′-5′oligoadenylate synthetase 3 Q2HJ14 797 26S protease regulatory subunit 4 (P26s4) P62191 798 26S proteasome non-ATPase regulatory subunit 7 P51665 799 26S proteasome non-ATPase regulatory subunit 14 O00487 800 40S ribosomal protein S16 P62249 801 40S ribosomal protein S6 (Phosphoprotein NP33) P62753 802 40S ribosomal protein S9 P46781 803 60S ribosomal protein L10a (CSA-19) P62906 804 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 Q16877 (6PF-2-K/Fru-2,6-P2ASE testis-type isozyme) 805 Cleavage and polyadenylation specificity factor, 73 kDa Q9UKF6 subunit (CPSF 73 kDa subunit) 806 A kinase anchor protein 10, mitochondrial precursor O43572 807 Actin, cytoplasmic 1 (Beta-actin) P60709 808 Activated T-cell marker CD109 Q6YHK3 809 Activin receptor type 2A precursor (EC 2.7.11.30) P27037 810 ADAM19 protein Q8TBU7 811 AP-1 complex subunit beta-1 (Adapter-related protein Q10567 complex 1 beta-1 subunit) (Beta-adaptin 1) 812 Adaptor-related protein NF01019537 Q9BYI8 813 Lung alpha/beta hydrolase protein 1 Q96SE0 814 Alpha-actinin-3 Q08043 815 Ankyrin-2 (Brain ankyrin) (Ankyrin-B) Q01484 816 Ankyrin repeat and SOCS box protein 17 Q8WXJ9 817 Anti-colorectal carcinoma heavy chain Q65ZQ1 818 APOBEC1 complementation factor (APOBEC1- Q9NQ94 stimulating protein) 819 Probable DNA dC->dU-editing enzyme APOBEC-3D (EC Q96AK3 3.5.4.—) 820 Apolipoprotein-L4 precursor (Apolipoprotein L-IV) Q9BPW4 821 Apoptosis stimulating of p53 protein 1 Q96KQ4 822 Nucleoporin 188 kDa (arachin) Q5SRE5 823 Protein ariadne-1 homolog (ARI-1) (Ubiquitin-conjugating Q9Y4X5 enzyme E2-binding protein 1) 824 Set1/Ash2 histone methyltransferase complex subunit Q9UBL3 ASH2 (ASH2-like protein) 825 ATP synthase F0 subunit 8 Q85KZ3 826 Splice isoform 2 of Q9H7F0 ATPase_family_homolog_up- Q9H7F0 regulated_in_senescence_cells_(—) 827 Probable phospholipid-transporting ATPase IA (EC Q9Y2Q0 3.6.3.1) (Chromaffin granule ATPase II) 828 ATP-binding cassette A10 Q8WWZ4 829 ATP-binding cassette sub-family A member 2 (ATP- Q9BZC7 binding cassette transporter 2) (ATP-binding cassette 2) 830 Autoantigen RCD8 Q6P2E9 831 xonemal dynein heavy chain 8 Q96JB1 832 Butyrophilin-like protein 8 precursor Q6UX41 833 Ubiquitin carboxyl-terminal hydrolase 20 (EC 3.1.2.15) Q9Y2K6 834 Bardet-Biedl syndrome 7 protein (BBS2-like protein 1) Q8IWZ6 835 Large proline-rich protein BAT2 (HLA-B-associated P48634 transcript 2) 836 Bcl-2 related ovarian killer Q9UL32 837 Lipopolysaccharide-responsive and beige-like anchor P50851 protein (CDC4-like protein) 838 Splice isoform 3 of P35612 P35612-3 839 UDP-GlcNAc:betaGal beta-1,3-N- Q9Y2A9 acetylglucosaminyltransferase 3 (EC 2.4.1.—) 840 Cell growth inhibiting protein 39 Q2TTR2 841 BH3-interacting domain death agonist (BID) P55957 842 CD48 antigen precursor (B-lymphocyte activation marker P09326 BLAST-1) 843 Bone morphogenetic protein receptor type-2 precursor (EC Q13873 2.7.11.30) 844 Bullous pemphigoid antigen 1, isoform 7 Q8WXK8 845 BRCA1 associated RING domain 1 variant Q53F80 846 Breast cancer type 2 susceptibility protein (Fanconi anemia P51587 group D1 protein) 847 Protein BRE (Brain and reproductive organ-expressed Q9NXR7 protein) (BRCA1/BRCA2-containing complex subunit 45) 848 Breast cancer 1 early onset Q3LRJ0 849 Breast and ovarian cancer susceptibility protein Q7KYU6 850 BTG2 protein (NGF-inducible anti-proliferative protein P78543 PC3) 851 Nuclear protein 5qNCA Q7LBC6 852 CAD protein [Includes: Glutamine-dependent carbamoyl- P27708 phosphate synthase (EC 6.3.5.5); Aspartate carbamoyltransferase (EC 2.1.3.2); Dihydroorotase (EC 3.5.2.3)] 853 Cadherin EGF LAG seven-pass G-type receptor 3 Q9NYQ7 precursor (Flamingo homolog 1) (hFmi1) (Multiple epidermal growth factor-like domains 2) (Epidermal growth factor-like 1) 854 Cadherin FIB3 Q6UW70 855 Integrin alpha-3 precursor (Galactoprotein B3) P26006 856 Calcineurin B homologous protein 2 (Hepatocellular O43745 carcinoma-associated antigen 520) 857 Calcium/calmodulin-dependent protein kinase II inhibitor Q7Z7J9 alpha (CaMKIINalpha) 858 Calpain-11 (EC 3.4.22.—) Q9UMQ6 859 Alpha-1 catenin (Cadherin-associated protein) (Alpha E- P35221 catenin) 860 Neural cell adhesion molecule variant Q59FY0 861 Ribosomal L1 domain-containing protein 1 (Cellular O76021 senescence-inhibited gene protein) 862 CENP-F kinetochore protein (Centromere protein F) P49454 (Mitosin) 863 Centaurin-delta 1 (Cnt-d1) (Arf-GAP, Rho-GAP, ankyrin Q8WZ64 repeat and pleckstrin homology domain-containing protein 2) 864 Centrosomal protein 2 (Centrosomal Nek2-associated Q9BV73 protein 1) (C-NAP1) 865 Pericentriol material 1 Q15154 866 Cervical cancer suppressor gene 5 Q8NFX8 867 T-complex protein 1 subunit zeta-2 Q92526 868 Chemokine-like factor (C32) Q9UBR5 869 Vacuolar protein sorting 13A Q96RL7 870 Chromodomain-helicase-DNA-binding protein 2 (EC O14647 3.6.1.—) 871 FERM domain-containing protein 6 Q96NE9 872 Putative protein C21orf56 Q9H0A9 873 Adiponutrin (iPLA2-epsilon) Q9NST1 884 Coatomer subunit gamma-2 Q9UBF2 875 Sodium/potassium/calcium exchanger 2 precursor Q9UI40 876 Exportin-1 (Chromosome region maintenance 1 protein O14980 homolog) 877 CUB and sushi domain-containing protein 3 precursor Q7Z407 878 Cullin-7 (CUL-7) Q14999 879 Cyclic AMP-dependent transcription factor ATF-4 P18848 880 S-phase kinase-associated protein 1A (Cyclin A/CDK2- P63208 associated protein p19) 881 Cyclin-A1 P78396 882 Cyclin M3, isoform 1 Q8NE01 883 Cystathionine beta-synthase human homolog of Q58H57 Cynomolgus monkey gene product 884 Cytochrome P450 2E1 (EC 1.14.14.1) P05181 885 Keratin, type II cytoskeletal 8 P05787 886 CPEB2 protein Q3B8N6 887 Probable ATP-dependent RNA helicase DDX5 (EC 3.6.1.—) P17844 888 Dedicator of cytokinesis protein 1 Q14185 889 Development and differentiation-enhancing factor 2 O43150 890 Probable ubiquitin carboxyl-terminal hydrolase FAF-Y (EC O00507 3.1.2.15) 891 G2 and S phase expressed protein 1 Q9NYZ3 892 HUMAN CDNA FLJ30829 fis, clone FEBRA2001790, Q96NI3 highly similar to Xenopus laevis RRM-containing protein SEB-4 mRNA 893 KIAA1799 protein Q96B95 894 Peroxisomal proliferator-activated receptor A-interacting Q9BYK8 complex 285 kDa protein (EC 3.6.1.—) (ATP-dependent helicase PRIC285) 895 HUMAN KIAA1922 Q96PW6 896 Transcription elongation factor SPT5 (DLC-1)(deleted in O00267 liver cancer-1) 897 DNA damage-binding protein 1 (Damage-specific DNA- Q16531 binding protein 1) 898 DNA excision repair protein ERCC-6 Q03468 899 DNA polymerase alpha subunit B (DNA polymerase alpha Q14181 70 kDa subunit) 900 DNA replication licensing factor MCM2 P49736 (Minichromosome maintenance protein 2 homolog) 901 DNA2-like homolog (EC 3.6.1.—) (DNA replication ATP- P51530 dependent helicase-like homolog) 902 Estrogen response element binding protein (cotton-top O77798 Tarmarin), DNA2-like homolog (human) 903 DNA damage-inducible transcript 3 (DDIT-3) (Growth P35638 arrest and DNA-damage-inducible protein GADD153) 904 DNA-directed RNA polymerase I largest subunit (EC O95602 2.7.7.6) 905 DnaJ homolog subfamily C member 1 Q96KC8 906 Splice isoform 2 of P35462 P35462-2 907 RuvB-like 2 (EC 3.6.1.—) (48-kDa TATA box-binding Q9Y230 protein-interacting protein) 908 DRE1_protein Q9NXT9 909 Dynactin-1 (150 kDa dynein-associated polypeptide) Q14203 910 Dynein heavy chain, cytosolic (DYHC) Q14204 911 Echinoderm microtubule associated protein-like 5 Q6UYC9 912 ECT2 protein (Epithelial cell-transforming sequence 2 Q9H8V3 oncogene) 913 Endothelial differentiation-related factor 1 (EDF-1) O60869 914 Developmentally-regulated endothelial cell locus 1 protein) O43854 915 Elongation factor 2 (EF-2) P13639 916 J domain protein C21orf55 Q9NX36 917 EMILIN-3 precursor (EMILIN-5) (Elastin microfibril Q9NT22 interface-located protein 5) 918 Synaptotagmin-like protein 4 (Exophilin-2) Q96C24 919 Enhancer of filamentation 1 (HEF1) Q14511 920 Band 4.1-like protein 3 (4.1B) (Differentially expressed in Q9Y2J2 adenocarcinoma of the lung protein 1) (DAL-1) 921 Epidermal growth factor receptor substrate 15 P42566 922 Epithelial membrane protein 3 (EMP-3) (YMP protein) P54852 923 Zyxin (Zyxin-2) Q15942 924 Eukaryotic translation initiation factor 4 gamma 1 Q04637 925 F-actin capping protein beta subunit P47756 926 Protocadherin Fat 2 precursor (hFat2) (Multiple epidermal Q9NYQ8 growth factor-like domains 1) 927 KIAA1752 protein Q9C0B1 928 Fc alpha/mu receptor Q8WWV6 929 Low affinity immunoglobulin gamma Fc region receptor P08637 III-A precursor (IgG Fc receptor III-2) 930 FYVE, RhoGEF and PH domain-containing protein 2 (Zinc Q7Z6J4 finger FYVE domain-containing protein 4) 931 Fibroblast growth factor receptor-like 1 precursor (FGF Q8N441 receptor-like protein 1) 932 Fibroblast growth factor receptor 4 precursor (EC 2.7.10.1) P22455 933 Fibroblast growth factor receptor 2 precursor (EC 2.7.10.1) P21802 (FGFR-2) 934 FK506-binding protein 7 precursor (EC 5.2.1.8) Q9Y680 935 Glomulin (FKBP-associated protein) (FK506-binding Q92990 protein-associated protein) 936 FKSG73 Q9BWW1 937 Flavin containing monooxygenase 3 isoform 2 variant Q53FW5 938 Protein flightless-1 homolog Q13045 939 Guanylate-binding protein 4 Q96PP9 940 Filamin-A (Alpha-filamin) (Filamin-1) (Endothelial actin- P21333 binding protein) 941 FLJ10101 protein Q8WU94 942 CDNA FLJ14503 fis, clone NT2RM1000252, weakly Q96T17 similar to H. sapiens E-MAP-115 mRNA 943 E2F8 protein Q5BKY4 944 Human Hypothetical protein Q2VPJ3 945 HUMAN CDNA FLJ34154 fis, clone FCBBF3013058 Q8NB70 946 Hypothetical protein FLJ43654 (Hypothetical protein Q6ZUJ4 C3orf62) 947 HUMAN CDNA FLJ46180 fis, clone TESTI4004031 Q6ZRQ5 948 Flotillin-2 (Epidermal surface antigen) (ESA) Q14254 949 Serine/threonine-protein kinase ATR (EC 2.7.11.1) (Ataxia Q13535 telangiectasia and Rad3-related protein) (FRAP-related protein 1) 950 Frizzled 5 precursor (Frizzled-5) Q13467 951 Fructose-bisphosphate aldolase C (EC 4.1.2.13) P09972 952 G protein pathway suppressor 1 isoform 1 variant Q53HS2 953 KiSS-1 receptor (KiSS-1R) (Kisspeptins receptor) Q969F8 (Metastin receptor) (G-protein coupled receptor 54) 954 Probable G-protein coupled receptor 55 Q9Y2T6 955 Probable G-protein coupled receptor 35 Q9HC97 956 G-protein coupled receptor family C group 5 member C Q9NQ84 precursor (Retinoic acid-induced gene 3 protein) 957 Leucine-rich repeat-containing G-protein coupled receptor O75473 5 precursor (Orphan G-protein coupled receptor HG38) (G- protein coupled receptor 49) (G-protein coupled receptor 67) 958 Probable G-protein coupled receptor 133 precursor (G- Q6QNK2 protein coupled receptor PGR25) 959 G1 to S phase transition protein 1 homolog (GTP-binding P15170 protein GST1-HS) 960 Gamma-aminobutyric-acid receptor alpha-6 subunit Q16445 precursor (GABA(A) receptor) 961 Ganglioside-induced differentiation-associated protein 1- Q96MZ0 like 1 (GDAP1-L1) 962 Gap junction alpha-5 protein (Connexin-40) (Cx40) P36382 963 GEM-interacting protein (GMIP) Q9P107 964 Golgin subfamily B member 1 (Giantin) Q14789 965 UDP-N-acetylhexosamine pyrophosphorylase (Antigen X) Q16222 966 Neutral alpha-glucosidase AB precursor (EC 3.2.1.84) Q14697 967 Probable dolichyl pyrophosphate Glc1Man9GlcNAc2 Q9BVK2 alpha-1,3-glucosyltransferase (EC 2.4.1.—) 968 Bifunctional aminoacyl-tRNA synthetase [Includes: P07814 Glutamyl-tRNA synthetase (EC 6.1.1.17) (Glutamate-- tRNA ligase); Prolyl-tRNA synthetase (EC 6.1.1.15) (Proline--tRNA ligase)] 969 Glycoprotein nmb-like protein Q8IXJ5 970 Prolactin-releasing peptide receptor (PrRP receptor) P49683 (PrRPR) (G-protein coupled receptor 10) 971 G protein-coupled receptor 112 Q5EGP2 972 Growth factor receptor-bound protein 14 (GRB14 adapter Q14449 protein) 973 GRIP and coiled-coil domain-containing protein 2 (Golgi Q8IWJ2 coiled coil protein GCC185) (CTCL tumor antigen se1-1) 974 GROS1-L protein Q9HC86 975 Growth hormone secretagogue receptor type 1 (GHS-R) Q92847 976 Glutathione S-transferase A4-4 (EC 2.5.1.18) O15217 977 GTP-binding protein Rhes (Ras homolog enriched in Q96D21 striatum) (Tumor endothelial marker 2) 978 GTP-binding protein Rit1 (Ras-like protein expressed in Q92963 many tissues) 979 VGFG2573 Q6UY45 980 Hypothetical protein HDLBP Q53QU2 981 Heat shock protein 75 kDa, mitochondrial precursor (HSP Q12931 75) (Tumor necrosis factor type 1 receptor-associated protein) 982 Heat shock protein apg-1 Q53ZP9 983 Tumor rejection antigen (Gp96) 1 Q5CAQ5 984 Heat-shock protein beta-3 (HspB3) (Heat shock 17 kDa Q12988 protein) 985 Low-density lipoprotein receptor-related protein 5 O75197 precursor 986 Regulator of telomere elongation helicase 1 (EC 3.6.1.—) Q9NZ71 (Helicase-like protein NHL) 987 Hematopoietic protein 1 Q52LW0 988 Heme oxygenase 1 (EC 1.14.99.3) (HO-1) P09601 989 Heparan sulfate glucosamine 3-O-sulfotransferase 5 (EC Q8IZT8 2.8.2.23) 990 Hepatocellular carcinoma-associated antigen 66 Q9NYH9 991 Melanoma-associated antigen E2 (MAGE-E2 antigen) Q8TD90 (Hepatocellular carcinoma-associated protein 3) 992 26S proteasome non-ATPase regulatory subunit 10 (26S O75832 proteasome regulatory subunit p28) Hepatocellular carcinoma-associated protein p28-II 993 Hephaestin Q5JUU1 994 HECT domain and RCC1-like domain-containing protein 2 O95714 (HERC2) 995 Heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP P22626 A2/hnRNP B1) 996 Heterogeneous nuclear ribonucleoprotein R (hnRNP R) O43390 997 HEXIM1 protein (HMBA-inducible) O94992 998 Histatin-1 precursor (Histidine-rich protein 1) P15515 999 Histone deacetylase 1 (HD1) Q13547 1000 Histone deacetylase 9 (HD9) (HD7B) (HD7) Q9UKV0 1001 Homeodomain-interacting protein kinase 2 (EC 2.7.11.1) Q9H2X6 1002 Cullin-2 (CUL-2) Q13617 1003 SWI/SNF-related matrix-associated actin-dependent O60264 regulator of chromatin subfamily A member 5 (EC 3.6.1.—) 1004 HUMAN HSPC027 26S proteasome non-ATPase Q9Y6E3 regulatory subunit 13 Synonyms 26S proteasome regulatory subunit S11 26S proteasome regulatory subunit p40.5 1005 Hypothetical protein (Novel protein HSPC117) Q9Y3I0 (DJ149A16.6 protein) (Hypothetical protein HSPC117) 1006 Claudin domain-containing protein 1 (Membrane protein Q9NY35 GENX-3745) Q9NY35 1007 Large neutral amino acids transporter small subunit 2 (L- Q9UHI5 type amino acid transporter 2) (hLAT2) 1008 Heterogeneous nuclear ribonucleoprotein C-like 1 (hnRNP O60812 core protein C-like 1) 1009 Ornithine decarboxylase (EC 4.1.1.17) (ODC) P11926 1010 Regulator of nonsense transcripts 2 (Nonsense mRNA Q9HAU5 reducing factor 2) (Up-frameshift suppressor 2 homolog) (hUpf2) 1011 ATX10_HUMAN Ataxin-10 Q9UBB4 1012 KIAA1833 protein Q569G6 1013 HUMAN UDP-GalNAc:betaGlcNAc beta 1,3- Q8NCR0 galactosaminyltransferase, polypeptide 2 (Beta 1,3-N- acetylgalactosaminyltransferase-II) (MGC39558) 1014 Hypothetical protein KIAA1033 Q2M389 1015 Activating signal cointegrator 1 complex subunit 3 (EC Q8N3C0 3.6.1.—) 1016 Delta-interacting protein A (Hepatitis delta antigen- Q15834 interacting protein A) (Coiled-coil domain-containing protein 85B) 1017 Hypothetical protein FLJ14466 Q96BP7 1018 Interferon-inducible double stranded RNA-dependent O75569 protein kinase activator A 1019 Hypothetical protein C9orf142 Q9BUH6 1020 Tetratricopeptide repeat protein 17 Q96AE7 1021 CDNA FLJ14058 fis, clone HEMBB1000554 Q9H7Z0 1022 Anaphase promoting complex subunit 13 Q9BS18 1023 Hypothetical protein CCDC60 Q8IWA6 1024 Sphingosine kinase 2 (EC 2.7.1.—) Q9NRA0 1025 Probable ATP-dependent RNA helicase DDX11 (EC Q96FC9 3.6.1.—) (DEAD/H box protein 11) (CHL1 homolog) (Keratinocyte growth factor-regulated gene 2 protein) (KRG-2) 1026 Protein KIAA0182 Q14687 1027 Ras GTPase-activating protein SynGAP (Synaptic Ras- Q96PV0 GTPase-activating protein 1) (Synaptic Ras-GAP 1) (Neuronal RasGAP) 1028 Fibrinogen C domain containing 1 Q8N539 1029 MGC39581 protein Q86XM0 1030 Bcl-2-like 13 protein (Mil1 protein) (Bcl-rambo) Q9BXK5 1031 Myosin head domain containing 1 Q96H55 1032 WD-repeat protein 51A Q8NBT0 1033 KIF27A (OTTHUMP00000021559) Q86VH2 1034 Inositol polyphosphate-5-phosphatase F, isoform 1 Q2T9J4 1035 Myopalladin Q96KF5 1036 Rho GTPase activating protein 12 Q5T2Y2 1037 Hypothetical protein DKFZp686D0630 Q7Z3C5 1038 Jumonji domain-containing protein 1C (Thyroid receptor- Q15652 interacting protein 8) (TRIP-8) 1039 Coatomer subunit beta (Beta-coat protein) (Beta-COP) P53618 1040 FLJ10462 fis, clone NT2RP1001494, weakly similar to Q9NVW8 MALE STERILITY PROTEIN 2 1041 Cell-cycle and apoptosis regulatory protein 1 Q6X935 1042 Telomere-associated protein RIF1 (Rap1-interacting factor Q5UIP0 1 homolog) 1043 F-box only protein 28 Q9NVF7 1044 CDNA FLJ10901 fis, clone NT2RP5003524 Q9NV65 1045 Acetoacetyl-CoA synthetase (EC 6.2.1.16) Q86V21 1046 Putative cell cycle control protein (DEP domain containing Q9NXZ0 1) 1047 Synaptopodin 2-like Q68A20 1048 CDNA FLJ36560 fis, clone TRACH2009340 Q8N9T8 1049 CDNA FLJ13330 fis, clone OVARC1001802 Q9H8Q0 1050 ATP-dependent RNA helicase DDX31 (EC 3.6.1.—) (DEAD Q9H8H2 box protein 31) (Helicain) 1051 Protein C14orf161 Q9H7T0 1052 Cysteine protease ATG4B (EC 3.4.22.—) (Autophagy- Q9Y4P1 related protein 4 homolog B) 1053 CDNA FLJ14526 fis, clone NT2RM1001139 Q96T08 1054 Hypothetical protein CCDC77 (CDNA FLJ14732 fis, clone Q9BR77 NT2RP3001969, weakly similar to TRICHOHYALIN) 1055 CDNA FLJ14790 fis, clone NT2RP4000973, weakly Q96K38 similar to PROBABLE PROTEIN DISULFIDE ISOMERASE P5 (EC 5.3.4.1) 1056 Keratin 24 Q2M2I5 1057 BCoR protein (BCL-6 corepressor) Q6W2J9 1058 Hypothetical protein FLJ20582 Q6IQ21 1059 Hypothetical protein FLJ22688 Q9BT04 1060 Hypothetical protein FLJ22944 Q9H5W3 1061 Zinc finger protein, subfamily 1A, 5- Q8TBE5 1062 Leucine-rich repeats and IQ motif containing 2 Q8IW35 1063 Hypothetical protein FLJ23749 Q8TEA0 1064 Hypothetical protein FLJ25336 http://www.expasy.org/sprot/userman.html AC lineQ96LP1 1065 Hypothetical protein FLJ25660 Q8N7G6 1066 CDNA FLJ30058 fis, clone ADRGL2000074, weakly Q96NU6 similar to RHO-GTPASE-ACTIVATING PROTEIN 6 1067 CDNA FLJ30106 fis, clone BNGH41000190, weakly Q96A82 similar to Rattus norvegicus schlafen-4 (SLFN-4) mRNA. 1068 Whirlin Q9P202 1069 CDNA FLJ31846 fis, clone NT2RP7000425, weakly Q96MV0 similar to MYOSIN HEAVY CHAIN, NONMUSCLE TYPE B 1070 FLJ32833 fis, clone TESTI2003228 Q96M43 1071 Guanine nucleotide-binding protein G(olf), alpha subunit P38405 (Adenylate cyclase-stimulating G alpha protein, olfactory type) 1072 CDNA FLJ33811 fis, clone CTONG2002095 Q8N279 1073 Transmembrane protein 16C Q9BYT9 1074 Zinc finger protein 31 (Zinc finger protein KOX29) (Zinc P17040 finger and SCAN domain-containing protein 20) (Zinc finger protein 360) 1075 Transmembrane 6 superfamily member 2 Q9BZW4 1076 CDNA FLJ90251 fis, clone NT2RM4000115 Q8NCH3 1077 CDNA FLJ90760 fis, clone THYRO1000061 Q8N2I4 1078 Tubulin--tyrosine ligase-like protein 12 Q14166 1079 KIAA0303 protein O15021 1080 Plexin-B2 precursor (MM1) O15031 1081 Zinc finger and BTB domain-containing protein 5 O15062 1082 Centrosome-associated protein 350 Q8WY20 1083 piccolo (Aczonin) Q9Y6V0 1084 KIAA0560 protein O60306 1085 KIAA0676 protein Q96H49 1086 Human homolog of Mus SLIT and NTRK-like protein 5 Q810B7 precursor 1087 Nischarin Q6PIB4 1088 FERM domain-containing protein 4A Q9P2Q2 1089 Leucine-rich repeats neuronal protein 1 precursor Q6UXK5 (Neuronal leucine-rich repeat protein 1) (NLRR-1) 1090 KIAA1512 protein Q9P216 1091 KIAA1598 protein Q9HCH4 1092 Phosphatidylinositol-3 phosphate 3-phosphatase adaptor Q96QU2 subunit 1093 KIAA1730 protein Q9C0D3 1094 KIAA1786 protein Q96JN9 1095 Hypothetical protein MGC20470 Q96EK3 1096 OACT1 protein Q86XC2 1097 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 Q16877 (6PF-2-K/Fru-2,6-P2ASE testis-type isozyme) 1098 IkappaB kinase complex-associated protein (IKK complex- O95163 associated protein) (p150) 1099 Immune receptor expressed on myeloid cells 2 Q7Z7I3 1100 High-affinity cAMP-specific and IBMX-insensitive 3′,5′- O60658 cyclic phosphodiesterase 8A (EC 3.1.4.17) 1101 Bone specific CMF608 Q6WRI0 1102 Importin alpha-7 subunit (Karyopherin alpha-6) O60684 1103 InaD-like protein (Inadl protein) (hINADL) (Pals1- Q8NI35 associated tight junction protein) (Protein associated to tight junctions) 1104 Nitric oxide synthase, inducible (EC 1.14.13.39) P35228 1105 Transcription elongation factor SPT5 (hSPT5) O00267 1106 Inositol-trisphosphate 3-kinase B (EC 2.7.1.127) (Inositol P27987 1,4,5-trisphosphate 3-kinase B) 1107 Type I inositol-3,4-bisphosphate 4-phosphatase (EC Q96PE3 3.1.3.66) (Inositol polyphosphate 4-phosphatase type I) 1108 Insulin receptor beta subunit Q9UCB7 1109 Insulin-like growth factor binding protein, acid labile Q8TAY0 subunit 1110 Integrin beta-4 precursor (GP150) (CD104 antigen) P16144 1111 Splice isoform 2 of P35462 P35462-2 1112 Interferon alpha 2 protein Q16055 1113 Interferon-induced protein with tetratricopeptide repeats 1 P09914 (IFIT-1)) (Interferon-induced 56 kDa protein) (IFI-56K) 1114 Interleukin-20 precursor (IL-20) (Four alpha helix cytokine Q9NYY1 Zcyto10) 1115 Steroid receptor RNA activator isoform 1 Q9HD15 1116 Intersectin-2 (SH3 domain-containing protein 1B) Q9NZM3 (SH3P18) (SH3P18-like WASP-associated protein) 11117 ITI-like protein (Inter-alpha (Globulin) inhibitor H5-like) Q6UXX5 1118 Gap junction alpha-5 protein (Connexin-40) P36382 1119 Kelch-like protein 8 Q9P2G9 1120 Keratin, type II cytoskeletal 1 (Cytokeratin-1) P04264 1121 ADAM 9 precursor (EC 3.4.24.—) (A disintegrin and Q13443 metalloproteinase domain 9) (Metalloprotease/disintegrin/cysteine-rich protein 9) (Myeloma cell metalloproteinase) 1122 Next to BRCA1 gene 1 protein (Neighbor of BRCA1 gene Q14596 1 protein) (Membrane component, chromosome 17, surface marker 2) (1A1-3B) 1123 Hypothetical protein DKFZp686K2075 Q6MZZ8 1124 KIAA0100 protein Q14667 1125 Pre-mRNA-splicing factor ATP-dependent RNA helicase Q92620 PRP16 (EC 3.6.1.—) (ATP-dependent RNA helicase DHX38) (DEAH box protein 38) 1126 KIAA0251 protein Q8TBS5 1127 HUMAN KIAA0342 protein O15050 1128 KIAA0357 protein O15064 1129 Hypothetical protein KIAA0372 Q6PGP7 1130 KIAA0377 splice variant 2 Q86TE7 1131 KIAA0386 protein Q9Y4F9 1132 HUMAN CTCL tumor antigen HD-CL-04 Q548S1 1133 Importin-13 (Imp13) (Ran-binding protein 13) O94829 1134 KIAA0769 protein O94868 1135 Hypothetical protein KIAA0863 Q6IQ32 1136 Zinc finger protein KIAA1196 - Q96KM6 1137 CRSP complex subunit 3 (Cofactor required for Sp1 Q9ULK4 transcriptional activation subunit 3) (Transcriptional coactivator CRSP130) (Vitamin D3 receptor-interacting protein complex 130 kDa component 1138 [Pyruvate dehydrogenase [lipoamide]]-phosphatase 2, Q9P2J9 mitochondrial precursor (EC 3.1.3.43) 1139 Protocadherin-10 precursor Q9P2E7 1140 Leucine-rich repeats and calponin homology (CH) domain Q5VUJ6 containing 2 1141 Ankyrin repeat domain 18B Q5W0G2 1142 Kin17 protein (HsKin17 protein) (KIN, antigenic O60870 determinant of recA protein homolog) 1143 Kinesin-like protein KIF13A (Kinesin-like protein RBKIN) Q9H1H9 1144 Putative RNA binding protein KOC O00425 1145 Keratin, type I cytoskeletal 18 (Cytokeratin-18) P05783 1146 Kv3.2d voltage-gated potassium channel Q86W09 1147 Lethal(3)malignant brain tumor-like protein (L(3)mbt-like) Q9Y468 (L(3)mbt protein homolog) 1148 Lactadherin precursor (Milk fat globule-EGF factor 8) Q08431 (MFG-E8) (HMFG) (Breast epithelial antigen BA46) (MFGM) 1149 Lamin-A/C (70 kDa lamin) P02545 1150 Laminin gamma-1 chain precursor (Laminin B2 chain) P11047 1151 Low-density lipoprotein receptor-related protein 5 O75197 precursor 1152 Leptin receptor precursor (LEP-R) (OB receptor) P48357 1153 Mitogen-activated protein kinase kinase kinase 13 (EC O43283 2.7.11.25) 1154 Leukemia virus receptor 2 Q08357 1155 Leukemia-associated protein with a CXXC domain Q8NFU7 1156 RNA-binding protein 6 (RNA-binding motif protein 6) P78332 (RNA-binding protein DEF-3) (Lung cancer antigen NY- LU-12) 1157 Lung cancer oncogene 5 Q7Z5Q7 1158 Heterogeneous nuclear ribonucleoprotein M (hnRNP M) P52272 1159 Macrophage migration inhibitory factor (MIF) P14174 (Phenylpyruvate tautomerase) (EC 5.3.2.1) 1160 Mitotic spindle assembly checkpoint protein MAD2B Q9UI95 (MAD2-like 2) (hREV7) 1161 Mitogen-activated protein kinase kinase kinase 4 (EC Q9Y6R4 2.7.11.25) (MAPK/ERK kinase kinase 4) 1162 Serine/threonine/tyrosine-interacting-like protein 1 (Dual- Q9Y6J8 specificity protein phosphatase 24) (Map kinase phosphatase-like protein MK-STYX) 1163 Microtubule-associated serine/threonine-protein kinase 2 Q6P0Q8 (EC 2.7.11.1) 1164 Matrix metalloprotease MMP-27 Q9H306 1165 MCM10 protein Q7L590 1166 Interferon-induced helicase C domain-containing protein 1 Q9BYX4 (EC 3.6.1.—) (Melanoma differentiation-associated protein 5) 1167 Melanoma ubiquitous mutated protein Q2TAK8 1168 Melanoma antigen family D, 2 Q5BJF3 1169 Melanocyte protein Pmel 17 precursor (Melanocyte P40967 lineage-specific antigen GP100) 1170 GPI-anchored protein p137 (p137GPI) (Membrane Q14444 component chromosome 11 surface marker 1) Cytoplasmic activation/proliferation-associated protein 1 1171 Hepatocyte growth factor receptor precursor (EC 2.7.10.1) P08581 (HGF receptor) (Scatter factor receptor) (SF receptor) (HGF/SF receptor) (Met proto-oncogene tyrosine kinase) 1172 Mitogen-activated protein kinase 14 (EC 2.7.11.24) Q16539 1173 Mitogen-activated protein kinase kinase kinase kinase 2 Q12851 (EC 2.7.11.1) (MAPK/ERK kinase kinase kinase 2) 1174 Mitotic kinesin-related protein Q96Q89 1175 Sperm-associated antigen 5 (Astrin) (Mitotic spindle- Q96R06 associated protein p126) 1176 Myeloid/lymphoid or mixed-lineage leukemia protein 4 Q9UMN6 (Trithorax homolog 2) 1177 Putative helicase MOV-10 (EC 3.6.1.—) (Moloney leukemia Q9HCE1 virus 10 protein) 1178 MOZ/CBP protein Q712H6 1179 Calgranulin B (Migration inhibitory factor-related protein P06702 14) (MRP-14) (P14) 1180 MUC2_HUMAN Mucin-2 precursor (Intestinal mucin 2) Q02817 1181 Mucin-5B precursor (Mucin 5 subtype B, tracheobronchial) Q9HC84 1182 Multiple PDZ domain protein (Multi PDZ domain protein O75970 1) (Multi-PDZ-domain protein 1) 1183 RUFY2 (Run and FYVE domain-containing protein Rabip4 Q8IW33 1184 Multidrug resistance-associated protein 7 Q8NHX7 1185 Multiple copies in a T-cell malignancies (Malignant T cell Q9ULC4 amplified sequence 1) (MCT1) 1186 DNA mismatch repair protein Msh3 P20585 1187 Protein CBFA2T2 (MTG8-like protein) (MTG8-related O43439 protein 1) (Myeloid translocation-related protein 1) 1188 Myomesin-1 (190 kDa titin-associated protein) (190 kDa P52179 connectin-associated protein 1189 Myosin heavy chain, cardiac muscle beta isoform (MyHC- P12883 beta) 1190 Myosin-13 (Myosin heavy chain, skeletal muscle, Q9UKX3 extraocular) (MyHC-eo) 1191 Tumor suppressor candidate 3 (N33 protein) Q13454 1192 Nebulin-related anchoring protein Q8TCH0 1193 Neural cell adhesion molecule 1, 1 P13592 1194 Neurotrimin precursor Q9P121 1195 Ninein Q8N4C6 1196 Notch homolog 2 Q5VTD0 1197 Neurogenic locus notch homolog protein 1 precursor P46531 (Notch 1) (hN1) (Translocation-associated notch protein TAN-1) [Contains: Notch 1 extracellular truncation; Notch 1 intracellular domain] 1198 Neurogenic locus notch homolog protein 3 precursor Q9UM47 (Notch 3) [Contains: Notch 3 extracellular truncation; Notch 3 intracellular domain] 1199 Neurogenic locus notch homolog protein 4 precursor Q99466 (Notch 4) (hNotch4) [Contains: Notch 4 extracellular truncation; Notch 4 intracellular domain] - 1200 Plexin-A1 precursor (Semaphorin receptor NOV) Q9UIW2 1201 HUMAN NPD011 Q9H2R7 1202 Nuclear autoantigen Sp-100 (Speckled 100 kDa) (Nuclear P23497 dot-associated Sp100 protein) 1203 Nuclear factor erythroid 2-related factor 1 (NF-E2-related Q14494 factor 1) (NFE2-related factor 1) (Nuclear factor, erythroid derived 2, like 1) (Transcription factor 11) (Transcription factor HBZ17) (Transcription factor LCR-F1) (Locus control region-factor 1) 1204 Nuclear factor of activated T-cells, cytoplasmic 1 (NFAT O95644 transcription complex cytosolic component) (NF-ATc1) 1205 Nuclear receptor coactivator 2 (NCoA-2) (Transcriptional Q15596 intermediary factor 2) 1206 Ubiquitin-like PHD and RING finger domain-containing Q96T88 protein 1 (EC 6.3.2.—) 1207 Nucleic acid helicase DDXx Q8IWW2 1208 Nucleoporin 62 kDa (NUP62 protein) Q6GTM2 1209 Nuclear pore complex protein Nup98-Nup96 precursor P52948 [Contains: Nuclear pore complex protein Nup98 (Nucleoporin Nup98) (98 kDa nucleoporin); 1210 Nucleoprotein TPR P12270 1211 Nuclear pore complex protein Nup107 P57740 1212 Nuclear pore complex protein Nup205 Q92621 1213 ODF2 protein Q6PJQ8 1214 Trophoblast glycoprotein precursor (5T4 oncofetal Q13641 trophoblast glycoprotein) 1215 Dynamin-like 120 kDa protein, mitochondrial precursor O60313 (Optic atrophy 1 gene protein) 1216 Orexin receptor type 2 (Ox2r) (Hypocretin receptor type 2) O43614 1217 Transmembrane emp24 domain-containing protein 10 P49755 precursor (Transmembrane protein Tmp21) 1218 Orphan nuclear receptor TR2 (Testicular receptor 2) P13056 1219 MKL/myocardin-like protein 1 (Myocardin-related Q969V6 transcription factor A) (MRTF-A) (Megakaryoblastic leukemia 1 protein) (Megacaryocytic acute leukemia protein) 1220 Ovarian cancer related tumor marker CA125 - Q8WXI7 1221 Oxysterol-binding protein-related protein 8 (OSBP-related Q9BZF1 protein 8) 1222 Centrosomal protein of 70 kDa (Cep70 protein) (p10- Q8NHQ1 binding protein) 1223 Leucine carboxyl methyltransferase 2 (EC 2.1.1.—) O60294 (p21WAF1/CIP1 promoter-interacting protein) 1224 F-box/LRR-repeat protein 5 (F-box and leucine-rich repeat Q9UKA1 protein 5) (F-box protein FBL4/FBL5) 1225 Inhibitor of growth protein 3 Q9NXR8 1226 P53 inducible protein Q9UN29 1227 DNA polymerase alpha catalytic subunit (EC 2.7.7.7) P09884 1228 Chloride intracellular channel protein 4 (Intracellular Q9Y696 chloride ion channel protein p64H1 1229 Paired mesoderm homeobox protein 2B (Paired-like Q99453 homeobox 2B) (PHOX2B homeodomain protein) (Neuroblastoma Phox) 1230 PRB3 protein P81489 1231 Protein patched homolog 1 (PTC1) (PTC) Q13635 1232 Rap guanine nucleotide exchange factor 2 (Neural RAP Q9Y4G8 guanine nucleotide exchange protein) (nRap GEP) (PDZ domain-containing guanine nucleotide exchange factor 1) (PDZ-GEF1) 1233 Pecanex-like protein 1 (Pecanex homolog) - Q96RV3 1234 GC-1-related estrogen receptor alpha coactivator short Q8TDE4 isoform 1235 PHD finger Q86U89 1236 Hypothetical protein DKFZp686C07187 Q6N038 1237 Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic P42338 subunit beta isoform (EC 2.7.1.153) (PI3-kinase p110 subunit beta) (PtdIns-3-kinase p110) 1238 Phosphodiesterase 8A, isoform 1 Q6P9H3 1239 Serine/threonine-protein kinase SMG1 (EC 2.7.11.1) Q96Q15 (SMG-1) (hSMG-1) (Lambda/iota protein kinase C- interacting protein) (Lambda-interacting protein) ( 1240 PiggyBac transposable element derived 3 Q8N328 1241 PIWIL3 protein Q7Z3Z3 1242 Homeobox protein PKNOX1 (PBX/knotted homeobox 1) P55347 1243 Transmembrane protein 115 (Protein PL6) Q12893 1244 Plakophilin-2 Q99959 1245 Plectin 6 Q6S380 1246 Plectin 1 (PLTN) (PCN) (Hemidesmosomal protein 1) Q15149 (HD1) 1247 Plexin B1; plexin 5; semaphorin receptor O43157 1248 Pleiotropic regulator 1 O43660 1249 Blood vessel epicardial substance (hBVES) (Popeye Q8NE79 domain-containing protein 1) (Popeye protein 1) 1250 Carboxypeptidase-like protein X2 precursor Q8N436 1251 YIF1B protein Q5BJH7 1252 Melanoma antigen preferentially expressed in tumors P78395 (Pr4eferentially expressed antigen of melanoma) (OPA- interacting protein 4) 1253 Splice isoform 2 of Q9H7F0 Q9H7F0-2 1254 P2Y purinoceptor 13 (P2Y13) (G-protein coupled receptor Q9BPV8 86) (G-protein coupled receptor 94) 1255 Putative pre-mRNA-splicing factor ATP-dependent RNA O43143 helicase DHX15 (EC 3.6.1.—) (DEAH box protein 15) (ATP-dependent RNA helicase #46) 1256 HUMAN RNA-binding protein 34 (RNA-binding motif P42696 protein 34) 1257 Prolyl 4-hydroxylase alpha-1 subunit precursor (EC P13674 1.14.11.2) (4-PH alpha-1) (Procollagen-proline, 2- oxoglutarate-4-dioxygenase alpha-1 subunit) 1258 Profilin-1 P07737 1259 Programmed cell death protein 5 (TFAR19 protein) (TF-1 O14737 cell apoptosis-related gene 19 protein) 1260 Propionyl-CoA carboxylase beta chain, mitochondrial P05166 precursor (EC 6.4.1.3) 1261 26S proteasome non-ATPase regulatory subunit 1 (26S Q99460 proteasome regulatory subunit RPN2) (26S proteasome regulatory subunit S1) (26S proteasome subunit p112) 1262 26S proteasome non-ATPase regulatory subunit 3 (26S O43242 proteasome regulatory subunit S3) (Proteasome subunit p58) 1263 Proteasome activator complex subunit 3 (Proteasome P61289 activator 28-gamma subunit) (PA28gamma) (PA28g) (Activator of multicatalytic protease subunit 3) (11S regulator complex gamma subunit) (REG-gamma) (Ki nuclear autoantigen) 1264 Protein C14orf166 Q9Y224 1265 Protein KIAA1219 Q86X10 1266 Protein KIAA1688 Q9C0H5 1267 Protein Plunc precursor (Palate lung and nasal epithelium Q9NP55 clone protein) (Lung-specific protein X) (Nasopharyngeal carcinoma-related protein) (Tracheal epithelium-enriched protein) (Secretory protein in upper respiratory tracts) 1268 Protein transport protein Sec23B Q15437 1269 Liprin-alpha-2 (Protein tyrosine phosphatase receptor type f O75334 polypeptide-interacting protein alpha-2) (PTPRF- interacting protein alpha-2) 1270 Protocadherin gamma A12 precursor (PCDH-gamma-A12) O60330 (Cadherin-21) (Fibroblast cadherin 3) 1271 Protocadherin gamma A10 precursor (PCDH-gamma-A10) Q9Y5H3 1272 Leucine carboxyl methyltransferase 2 (EC 2.1.1.—) O60294 (p21WAF1/CIP1 promoter-interacting protein) 1273 KIAA1636 protein Q9HCD6 1274 Probable G-protein coupled receptor 160 Q9UJ42 1275 Protein C21orf45 Q9NYP9 1276 Periodic tryptophan protein 2 homolog Q15269 1277 Rab-like protein 2B Q9UNT1 1278 Cell cycle checkpoint protein RAD17 (hRad17) (RF- O75943 C/activator 1 homolog) 1279 DNA repair protein RAD50 (EC 3.6.—.—) (hRAD50) Q92878 1280 Ras GTPase-activating protein 1 (GTPase-activating P20936 protein) (GAP) (Ras p21 protein activator) (p120GAP) (RasGAP) 1281 Ras guanine nucleotide exchange factor 2 Q9UK56 1282 Ras-GTPase-activating protein-binding protein 1 (EC Q13283 3.6.1.—) (ATP-dependent DNA helicase VIII) (GAP SH3- domain-binding protein 1) (G3BP-1) (HDH-VIII) 1283 Ras-related protein Rab-27A (Rab-27) (GTP-binding P51159 protein Ram) 1284 Ras-related protein Rab-3D O95716 1285 Nuclear pore complex protein Nup107 (Nucleoporin P57740 Nup107) (107 kDa nucleoporin) 1286 Receptor-interacting factor 1 Q86XS4 1287 Regulating synaptic membrane exocytosis protein 3 (Nim3) Q9UJD0 (Rab-3 interacting molecule 3) (RIM 3) (RIM3 gamma) 1288 Regulator of G protein signaling protein (Regulator of G- Q86UV0 protein signalling like 1) 1289 MHC class II regulatory factor RFX1 (RFX) (Enhancer P22670 factor C) (EF-C) 1290 Retinoblastoma-associated protein (PP110) (P105-RB) P06400 1291 Roundabout homolog 3 precursor (Roundabout-like protein Q96MS0 3) 1292 Retinoblastoma-associated protein HEC (Kinetochore O14777 associated 2) 1293 Retinoblastoma-associated protein RAP140 Q9UK61 1294 AT-rich interactive domain-containing protein 4A (ARID P29374 domain-containing protein 4A) (Retinoblastoma-binding protein 1) 1295 Jumonji/ARID domain-containing protein 1A P29375 (Retinoblastoma-binding protein 2) (RBBP-2) 1296 RhoGTPase regulating protein variant ARHGAP20-1ad Q6RJU5 1297 40S ribosomal protein S4, Y isoform 2 Q8TD47 1298 RNA binding motif Q13380 1299 RNA binding protein (Autoantigenic, hnRNP-associated Q2M365 with lethal yellow), long isoform - 1300 RNA-binding protein Q8NI52 1301 Ro ribonucleoprotein-binding protein 1 (SIAHBP1 protein) Q9UHX1 1302 HUMAN OTTHUMP00000030902 Q5JYR6 1303 Ryanodine receptor 2 (Cardiac muscle-type ryanodine Q92736 receptor) (RyR2) (RYR-2) (Cardiac muscle ryanodine receptor-calcium release channel) (hRYR-2) 1304 SEC14-like protein 1 Q92503 1305 Secreted and transmembrane protein 1 precursor (Protein Q8WVN6 K12) 1306 Neudesin precursor (Neuron-derived neurotrophic factor) Q9UMX5 1307 P-selectin glycoprotein ligand 1 precursor (PSGL-1) Q14242 (Selectin P ligand) (CD162 antigen) 1308 Semaphorin-6D precursor Q8NFY4 1309 Serine/threonine/tyrosine-interacting protein (Protein Q8WUJ0 tyrosine phosphatase-like protein) 1310 Olfactory receptor 8G5 (Olfactory receptor OR11-298) Q8NG78 1311 Shb-like adapter protein, Shf Q7M4L6 1312 Signal transducer and activator of transcription 1-alpha/beta P42224 (Transcription factor ISGF-3 components p91/p84) STAT1 1313 Signal transducer and activator of transcription 3 (Acute- P40763 phase response factor) 1314 40S ribosomal protein S7 P62081 1315 60S ribosomal protein L35 P42766 1316 60S ribosomal protein L7 P18124 1317 Thrombospondin-2 precursor P35442 1318 C3 and PZP-like alpha-2-macroglobulin domain containing 8 Q8IZJ3 1319 ATP-binding cassette sub-family F member 2 (Iron- Q9UG63 inhibited ABC transporter 2) 1320 Ribosome biogenesis protein BOP1 (Block of proliferation Q14137 1 protein) 1321 CDNA FLJ13765 fis, clone PLACE4000128, weakly Q9H8C5 similar to Mus musculus putative transcription factor mRNA 1322 CD200 cell surface glycoprotein receptor isoform 2 variant 2 Q6Q8B3 1323 LRRC58 protein Q96CX6 1324 Claudin-6 (Skullin 2) P56747 1325 T-box transcription factor TBX18 (T-box protein 18) O95935 1326 INTS7 protein Q8WUH5 1327 FRAS1-related extracellular matrix protein 2 precursor Q5SZK8 (ECM3 homolog) 1328 Zinc finger protein 318 (Endocrine regulatory protein) Q5VUA4 1329 Eukaryotic translation initiation factor 3 subunit 8 (eIF3 Q99613 p110) (eIF3c) 1330 HUMAN LOC196394 protein Q8IY45 1331 Hypothetical protein FLJ44216 Q8NDZ2 1332 Heat shock protein HSP 90-beta (HSP 84) (HSP 90) P08238 1333 Sarcoma antigen NY-SAR-41 (NY-SAR-41) Q5T9S5 1334 Protein FAM86A Q96G04 1335 Ras-like family 11 member A (OTTHUMP00000018162) Q6T310 1336 Keratin, type I cytoskeletal 18 (Cytokeratin-18) (CK-18) P05783 1337 U3 small nucleolar RNA-associated protein 14 homolog A Q9BVJ6 (Antigen NY-CO-16) 1338 Hypothetical protein DKFZp781D1722 Q68DM0 1339 Chromosome-associated kinesin KIF4A (Chromokinesin) O95239 1340 Kinesin-like protein KIF6 Q6ZMV9 1341 Myosin-10 (Myosin heavy chain, nonmuscle IIb) P35580 (Nonmuscle myosin heavy chain IIb) 1342 Hypothetical protein C17orf57 Q8IY85 1343 Similar to peptide N-glycanase homolog (S. cerevisiae) Q9BVR8 1344 Peptidyl-prolyl cis-trans isomerase A (EC 5.2.1.8) P62937 1345 Serpin A13 precursor Q6UXR4 1346 40S ribosomal protein SA (p40) (34/67 kDa laminin P08865 receptor) (Colon carcinoma laminin-binding protein) (NEM/1CHD4) (Multidrug resistance-associated protein MGr1-Ag) 1347 N-acetylglucosamine-1-phosphotransferase subunit gamma Q9UJJ9 precursor 1348 Liprin-beta-1 (Protein tyrosine phosphatase receptor type f Q86W92 polypeptide-interacting protein-binding protein 1) 1349 40S ribosomal protein S3a P61247 1350 40S ribosomal protein S3a P61247 1351 LOC124512 protein (Fragment) Q86XA0 1532 Hypothetical protein MGC26744 Q96KX1 1535 Hypothetical protein LOC122258 Q96KW9 1354 Sulfiredoxin-1 (EC 1.8.98.2) Q9BYN0 1355 Basalin Q5QJ38 1356 Protein FAM86A Q96G04 1357 Transmembrane protein 16F Q4KMQ2 1358 TEB4 protein O14670 1359 SLC10A5 Q5PT55 1360 Serine/threonine-protein kinase SNF1-like kinase 1 (EC P57059 2.7.11.1) 1361 LOC391257 protein Q6P094 1362 Zinc finger protein 161 (Putative transcription factor DB1) Q14119 1363 Slit homolog 2 protein precursor (Slit-2) O94813 1364 FYN-binding protein (FYN-T-binding protein) O15117 1365 Jumonji/ARID domain-containing protein 1C (SmcX P41229 protein) (Xe169 protein) 1366 Jumonji/ARID domain-containing protein 1D (SmcY Q9BY66 protein) (Histocompatibility Y antigen) 1367 Monocarboxylate transporter 3 (MCT 3) O95907 1368 Solute carrier family 4 sodium bicarbonate cotransporter- Q6U841 like member 10 - 1369 Sorting nexin 14, isoform a Q6NUI7 1370 Sorting nexin-4 O95219 1371 Spectrin beta chain, brain 4 (Spectrin, non-erythroid beta Q9NRC6 chain 4) 1372 Spermatogenesis-associated protein 7 (Spermatogenesis- Q9P0W8 associated protein HSD3) 1373 Non-POU domain-containing octamer-binding protein Q15233 (NonO protein) (54 kDa nuclear RNA- and DNA-binding protein) (p54(nrb)) (p54nrb) (55 kDa nuclear protein) 1374 Cohesin subunit SA-1 (Stromal antigen 1) (SCC3 homolog Q8WVM7 1) 1375 Steroid receptor RNA activator isoform 1 Q9HD15 1376 Structure-specific recognition protein 1 (SSRP1) Q08945 (Recombination signal sequence recognition protein) (T160) (Chromatin-specific transcription elongation factor 80 kDa subunit) 1377 Suppressor of hairy wing homolog 2 (5′OY11.1) (Zinc Q86YH2 finger protein 632) 1378 Transcription elongation factor SPT5 (hSPT5) (DRB O00267 sensitivity-inducing factor large subunit) (DSIF large subunit) (DSIF p160) (Tat-cotransactivator 1 protein) (Tat- CT1 protein) - 1379 Synaptogyrin-3 O43761 1380 Synaptojanin-2-binding protein (Mitochondrial outer P57105 membrane protein 25) 1381 Synemin Q8TE61 1382 Talin-1 Q9Y490 1383 TAR RNA loop binding protein (TAR (HIV) RNA binding Q13395 protein 1) 1384 Taste receptor type 2 member 3 (T2R3) Q9NYW6 1385 Taste receptor type 2 member 40 (T2R40) (T2R58) (G- P59535 protein coupled receptor 60) 1386 Oxidoreductase HTATIP2 (EC 1.1.1.—) (HIV-1 TAT- Q9BUP3 interactive protein 2) 1387 Transcription initiation factor TFIID subunit 6 P49848 (Transcription initiation factor TFIID 70 kDa subunit) (TAF(II)70) (TAFII-70) (TAFII-80) (TAFII80) 1388 TRA@ protein Q6PIP7 1389 T-complex protein 1 subunit beta (TCP-1-beta) (CCT-beta) P78371 1390 Telomerase-binding protein EST1A (Ever shorter Q86US8 telomeres 1A) (Telomerase subunit EST1A) (EST1-like protein A) (hSmg5/7a) 1391 Tumor endothelial marker 6 (Hypothetical protein TEM6) Q96PE0 1392 Ras GTPase-activating-like protein IQGAP2 Q13576 1393 Tetratricopeptide repeat protein 15 (TPR repeat protein 15) Q8WVT3 1394 Myosin-18A (Myosin XVIIIa) (Myosin containing PDZ Q92614 domain) (Molecule associated with JAK3 N-terminus) (MAJN) 1395 Polycystic kidney and hepatic disease 1 precursor Q8TCZ9 (Fibrocystin) 1396 TMC4 protein Q7Z5M3 1397 MDC-3.13 isoform 1 (TNFAIP8 protein) Q9UER5 1398 Toll-like receptor 8 precursor Q9NR97 1399 Tolloid-like protein 1 precursor (EC 3.4.24.—) O43897 1400 DNA topoisomerase I, mitochondrial precursor (EC Q969P6 5.99.1.2) (TOP1mt) 1401 PAP associated domain-containing protein 5 (EC 2.7.7.—) Q8NDF8 (Topoisomerase-related function protein 4-2) (TRF4-2) 1402 Plastin-3 (T-plastin) P13797 1403 Translocated promoter region (To activated MET Q5SWY0 oncogene) 1404 P2Y purinoceptor 13 (P2Y13) (G-protein coupled receptor Q9BPV8 86) (G-protein coupled receptor 94) 1405 Transcript Y 5 Q9BXH6 1406 Transcription factor Sp4 (SPR-1) Q02446 1407 Transcription initiation factor TFIID subunit 1 (EC P21675 2.7.11.1) (Transcription initiation factor TFIID 250 kDa subunit) (TAF(II)250) (TAFII-250) (TAFII250) (TBP- associated factor 250 kDa) (p250) (Cell cycle gene 1 protein) 1408 Transcriptional repressor CTCFL (CCCTC-binding factor) Q8NI51 (Brother of the regulator of imprinted sites) (Zinc finger protein CTCF-T) (CTCF paralog 1409 Transducer of regulated CREB protein 3 Q6UUV7 1410 Transmembrane channel-like protein 4 Q7Z404 1411 Transcription initiation factor TFIID subunit 6 P49848 (Transcription initiation factor TFIID 70 kDa subunit) (TAF(II)70) (TAFII-70) (TAFII-80) (TAFII80) 1412 Trophinin-associated protein (Tastin) (Trophinin-assisting Q12815 protein) 1413 Tryptophanyl-tRNA synthetase (EC 6.1.1.2) (Tryptophan-- P23381 tRNA ligase) (TrpRS) (IFP53) (hWRS) 1414 Tubulin, gamma complex associated protein 3 Q5T9Y2 1415 Tumor necrosis factor ligand superfamily member 6 (Fas P48023 antigen ligand) (Fas ligand) (CD178 antigen) (CD95L protein) (Apoptosis antigen ligand) (APTL) [Contains: Tumor necrosis factor ligand superfamily member 6, membrane form 1416 Tumor necrosis factor, alpha-induced protein 1, endothelial Q13829 (B12 protein) 1417 Netrin receptor DCC precursor (Tumor suppressor protein P43146 DCC) (Colorectal cancer suppressor) 1418 Adipocyte-derived leucine aminopeptidase precursor (EC Q9NZ08 3.4.11.—) (A-LAP) (ARTS-1) (Aminopeptidase PILS) (Puromycin-insensitive leucyl-specific aminopeptidase) (PILS-AP) (Type 1 tumor necrosis factor receptor shedding aminopeptidase 1419 U1 small nuclear ribonucleoprotein A (U1 snRNP protein P09012 A) (U1A protein) (U1-A 1420 U6 snRNA-associated Sm-like protein LSm8 O95777 1421 Ubiquitin-protein ligase E3A (EC 6.3.2.—) (E6AP ubiquitin- Q05086 protein ligase) (Oncogenic protein-associated protein E6- AP) (Human papillomavirus E6-associated protein) 1422 Ubiquitin carboxyl-terminal hydrolase 3 (EC 3.1.2.15) Q9Y6I4 (Ubiquitin thioesterase 3) (Ubiquitin-specific-processing protease 3) (Deubiquitinating enzyme 3) 1423 UBX domain-containing protein 2 Q92575 1424 UNC93 homolog B1 (UNC-93B protein) (hUNC93B1) Q9H1C4 1425 Splice isoform 5 of Q9H171 Q9H171-5 1426 CDNA FLJ46282 fis, clone TESTI4031066 Q6ZRK6 1427 CCDC73 protein Q6P5Q7 1428 Caspase recruitment domain-containing protein 10 (CARD- Q9BWT7 containing MAGUK protein 3) (Carma 3) 1429 Chromatin-specific transcription elongation factor FACT Q9Y5B9 140 kDa subunit 1430 Beta-defensin 120 precursor Q8N689 1431 Alpha-catulin (Catenin alpha-like protein 1) (Alpha- Q9UBT7 catenin-related protein) 1432 Ribonuclease III (EC 3.1.26.3) (RNase III) Q9NRR4 1433 Seizure related 6 homolog Q53EL9 1434 Granulocyte colony-stimulating factor precursor (G-CSF) P09919 (Pluripoietin) (Filgrastim) (Lenograstim) 1435 Lysyl-tRNA synthetase Q9HB23 1436 Protein C6orf130 Q9Y530 1437 Melanophilin (Exophilin-3) (Synaptotagmin-like protein Q9BV36 2a) (Slp homolog lacking C2 domains a) 1438 Novel protein (Possible ortholog of mouse Q5VTR6 phosphoinositide-3-kinase adaptor protein 1 (Pik3ap1) 1439 AER61 glycosyltransferase Q6P985 1440 Heat shock protein HSP 90-alpha (HSP 86) P07900 1441 60S ribosomal protein L19 P84098 1442 PDZ domain-containing protein 11 Q5EBL8 1443 Dedicator of cytokinesis 11-; Cdc42-associated guanine Q5JSL3 nucleotide exchange factor ACG/DOCK11 1444 Hypothetical protein FLJ26930 Q6ZNX6 1445 Laminin gamma-1 chain precursor (Laminin B2 chain) P11047 1446 ATP-binding cassette transporter sub-family C member 11 Q96J66 (Multidrug resistance-associated protein 8) 1447 Uridine/cytidine kinase-like 1 Q9NWZ5 1448 Butyrophilin-like protein 8 precursor Q6UX41 1449 Endothelial cell-selective adhesion molecule precursor Q96AP7 1450 Poly(A)-specific ribonuclease PARN (EC 3.1.13.4) O95453 (Polyadenylate-specific ribonuclease) (Deadenylating nuclease) (Deadenylation nuclease) 1451 Voltage-gated potassium channel KCNA7 Q96RP8 1452 F-box protein 11 Q52ZP1 1453 rythrocyte membrane protein band 4.1 like 5 Q7Z5S1 1454 CDNA FLJ45015 fis, clone BRAWH3014639 Q6ZT30 1455 FAM13A1_v2 protein Q24JP0 1456 Hypothetical protein FLJ26432 Q6ZP70 1457 VPS13D-1A protein Q709C5 1458 Coagulation factor VIII precursor (Procoagulant P00451 component) (Antihemophilic factor) (AHF) 1459 NFX1-type zinc finger-containing protein 1 Q9P2E3 1460 Polymerase I and transcript release factor (PTRF protein) Q6NZI2 1461 T-complex protein 1 subunit epsilon (TCP-1-epsilon) P48643 (CCT-epsilon) 1462 Probable ATP-dependent RNA helicase DDX27 (EC Q96GQ7 3.6.1.—) (DEAD box protein 27) 1463 HSCARG Q9HBL8 1464 CDNA FLJ43956 fis, clone TESTI4015681 Q6ZU72 1465 Mitochondrial-processing peptidase alpha subunit, Q10713 mitochondrial precursor (EC 3.4.24.64) (Alpha-MPP) 1466 CDNA FLJ45287 fis, clone BRHIP3002124 Q6ZSR0 1467 Hypothetical protein C12orf62 Q96I36 1468 VPS13D-2A protein Q709C4 1469 CDNA FLJ32009 fis, clone NT2RP7009498, weakly Q96DN2 similar to FIBULIN-1, ISOFORM A 1470 Transient receptor potential cation channel subfamily V Q9HBA0 member 4 (TrpV4) (osm-9-like TRP channel 4) (OTRPC4) (Vanilloid receptor-like channel 2) (Vanilloid receptor-like protein 2) (VRL-2) 1471 Vascular endothelial growth factor D precursor (VEGF-D) O43915 (c-fos-induced growth factor) (FIGF) 1472 Vascular endothelial growth factor receptor 1 precursor P17948 (EC 2.7.10.1) (VEGFR-1) (Vascular permeability factor receptor) (Tyrosine-protein kinase receptor FLT) (Flt-1) (Tyrosine-protein kinase FRT) (Fms-like tyrosine kinase 1) 1473 Proto-oncogene C-crk (P38) (Adapter molecule crk) P46108 1474 VDUP1 protein (Thioredoxin interacting protein) Q9H3M7 1475 Vimentin P08670 1476 HUMAN CTCL tumor antigen HD-CL-06 (Vimentin Q548L2 variant) 1477 Vinculin (Metavinculin) P18206 1478 Integrin alpha-3 precursor (Galactoprotein B3) (GAPB3) P26006 (VLA-3 alpha chain) (FRP-2) (CD49c antigen) [Contains: Integrin alpha-3 heavy chain; Integrin alpha-3 light chain] 1479 Voltage-dependent T-type calcium channel alpha-1H O95180 subunit (Voltage-gated calcium channel alpha subunit Cav3.2) (Low-voltage-activated calcium channel alpha1 3.2 subunit) 1480 Wiskott-Aldrich syndrome protein family member 4 Q8IV90 (WASP-family protein member 4) 1481 ATP synthase coupling factor 6, mitochondrial precursor P18859 (EC 3.6.3.14) (ATPase subunit F6) 1482 Proto-oncogene protein Wnt-3 precursor P56703 1483 Amyloid beta A4 precursor protein-binding family A Q99767 member 2 (Neuron-specific X11L protein) (Neuronal Munc18-1-interacting protein 2) (Mint-2) (Adapter protein X11beta) 1484 Zinc finger CCHC domain-containing protein 5 Q8N8U3 1485 Myeloid/lymphoid or mixed-lineage leukemia (Trithorax Q59FF2 homolog, Drosophila) variant 1486 Zinc finger protein DZIP1 (DAZ-interacting protein 1/2) Q86YF9 1487 Hypothetical protein DKFZp761O1618 Q69YS5 1488 ATP-binding cassette sub-family F member 2 (Iron- Q9UG63 inhibited ABC transporter 2) 1489 Ribosome biogenesis protein BOP1 (Block of proliferation Q14137 1 protein) 1490 CDNA FLJ13765 fis, clone PLACE4000128 Q9H8C5 1491 NDRG1 protein (N-myc downstream regulated gene 1 Q92597 protein) 1492 Pre-mRNA splicing factor ATP-dependent RNA helicase Q92620 PRP16 1493 Nesprin 2 (Nuclear envelope spectrin repeat protein 2) Q9NU50 1494 Adenomatous polyposis coli P25054 1495 Ubiquitin conjugating enzyme E2 P49459 1496 B cell receptor-associated protein BAP31 (CDM protein) P5572 6c6-AG 1497 Topoisomerase II-alpha P11388 1498 Topoisomerase II beta Q02880 1499 Integrin beta8 subunit precursor P26012 1500 Replication Protein A P27694 1501 Abl Binding protein 3 U31089 1502 Cyclin I Q14094 1503 Cell Division Control Protein 2 (CDC2) P06493 1504 Septin 2 (NEDD5) Q15019 1505 STAT1 alpha/beta P42224 1506 LDL Receptor-related protein (LRP) Q07954 1507 TACE (ADAM17) NP-068604 1508 Junction plakoglobin (gamma catenin) P14923 1509 EDDR1 Q08345 1510 IP3 receptor type II Q14571 1511 Melanoma-associated antigen D2 (MAGE-D2 antigen) Q9UNF1 (MAGE-D) (Breast cancer-associated gene 1 protein) (BCG-1) (11B6) (Hepatocellular carcinoma-associated protein JCL-1) 1512 Melanoma-associated antigen 4 (MAGE-4 antigen) P43358 (MAGE-X2) (MAGE-41) 1513 HUMAN Retinoblastoma-like protein 2 (130 kDa Q08999 retinoblastoma-associated protein) (PRB2) (P130) (RBR-2) 

1. A method for eliciting a CTL response against tumor cells presenting at least one of the following epitopic peptides: SEQ ID NO: 1516, 1517, 1519, 1521, 1527, 1528, or 1529 in a subject, comprising administering to said subject a composition comprising at least one polypeptide comprising an epitopic peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1516, 1517, 1519, 1521, 1527, 1528, and 1529 in an amount sufficient to induce a CTL response to said tumor cells.
 2. The method of claim 1, wherein said composition further comprises an adjuvant.
 3. The method of claim 2, wherein said adjuvant is selected from the group consisting of complete Freund's adjuvant, incomplete Freund's adjuvant, Montanide ISA-51, LAG-3, aluminum phosphate, aluminum hydroxide, alum, and saponin.
 4. The method of claim 1, wherein said composition further comprises a cytokine.
 5. The method of claim 4, wherein said cytokine is GM-CSF.
 6. The method of claim 1, wherein said composition further comprises a vehicle.
 7. The method of claim 6, where said vehicle is selected from the group consisting of a liposome, an immunostimulating complex (ISCOM), and slow-releasing particles.
 8. The method of claim 7, wherein said liposome comprises an emulsion, a foam, a micelle, an insoluble monolayer, a liquid crystal, a phospholipid dispersion, or a lamellar layer.
 9. The method of claim 1, wherein said polypeptide consists of an amino acid sequence selected from the group consisting of SEQ ID NO: 1516, 1517, 1519, 1521, 1527, 1528, and
 1529. 10. The method of claim 1 wherein said tumor cells are part of a carcinoma.
 11. The method of claim 1 wherein said tumor cells are part of an ovarian carcinoma.
 12. The method of claim 1 wherein said polypeptide comprises at least two epitopic peptides.
 13. The method of claim 12 wherein said polypeptide comprises at least three epitopic peptides.
 14. The method of claim 12, wherein said polypeptide comprises a first epitopic peptide and a second epitopic peptide, wherein said first epitopic peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1516, 1517, 1519, 1521, 1527, 1528, and 1529 and said second epitopic peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 1516, 1517, 1519, 1521, 1527, 1528, and
 1529. 